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Review

Human NK cells and cancer

Claudia Cantonia Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy;b Laboratory of Clinical and Experimental Immunology, Integrated Department of Services and Laboratories, IRCCS Istituto Giannina Gaslini, Genoa, ItalyORCID Iconhttps://orcid.org/0000-0001-6471-1424View further author information
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Michela Falcob Laboratory of Clinical and Experimental Immunology, Integrated Department of Services and Laboratories, IRCCS Istituto Giannina Gaslini, Genoa, ItalyORCID Iconhttps://orcid.org/0000-0002-0317-9830View further author information
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Massimo Vitalec UO Pathology and Experimental Immunology, IRCCS Ospedale Policlinico, San Martino, Genova, ItalyORCID Iconhttps://orcid.org/0000-0001-5372-7885View further author information
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Gabriella Pietraa Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy;c UO Pathology and Experimental Immunology, IRCCS Ospedale Policlinico, San Martino, Genova, ItalyORCID Iconhttps://orcid.org/0000-0002-7080-531XView further author information
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Enrico Munarid Pathology Unit, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, ItalyORCID Iconhttps://orcid.org/0000-0002-3867-6685View further author information
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Daniela Pendec UO Pathology and Experimental Immunology, IRCCS Ospedale Policlinico, San Martino, Genova, ItalyORCID Iconhttps://orcid.org/0000-0003-1565-451XView further author information
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Maria Cristina Mingaria Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy;c UO Pathology and Experimental Immunology, IRCCS Ospedale Policlinico, San Martino, Genova, ItalyORCID Iconhttps://orcid.org/0000-0001-6998-5459View further author information
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Simona Sivoria Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy;e IRCCS Ospedale Policlinico, San Martino, Genova, ItalyORCID Iconhttps://orcid.org/0000-0003-1279-1172View further author information
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Lorenzo Morettaf Tumor Immunology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, ItalyCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0003-4658-1747View further author information
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Article: 2378520 | Received 29 Apr 2024, Accepted 05 Jul 2024, Published online: 16 Jul 2024

References

  • Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, Coussens LM, Gabrilovich DI, Ostrand-Rosenberg S, Hedrick CC. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541–18. doi: 10.1038/s41591-018-0014-x.
  • Ljunggren HG, Karre K. In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today. 1990;11:237–244. doi: 10.1016/0167-5699(90)90097-s.
  • Moretta A, Bottino C, Vitale M, Pende D, Biassoni R, Mingari MC, Moretta L. Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol. 1996;14(1):619–648. doi: 10.1146/annurev.immunol.14.1.619.
  • Long EO, Burshtyn DN, Clark WP, Peruzzi M, Rajagopalan S, Rojo S, Wagtmann N, Winter CC. Killer cell inhibitory receptors: diversity, specificity, and function. Immunol Rev. 1997;155(1):135–144. doi: 10.1111/j.1600-065x.1997.tb00946.x.
  • Lanier LL. Natural killer cells: from no receptors to too many. Immunity. 1997;6(4):371–378. doi: 10.1016/s1074-7613(00)80280-0.
  • Colonna M. Specificity and function of immunoglobulin superfamily NK cell inhibitory and stimulatory receptors. Immunol Rev. 1997;155(1):127–133. doi: 10.1111/j.1600-065x.1997.tb00945.x.
  • Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol. 2005;5(3):201–214. doi: 10.1038/nri1570.
  • Tomasello E, Blery M, Vely F, Vivier E. Signaling pathways engaged by NK cell receptors: double concerto for activating receptors, inhibitory receptors and NK cells. Semin Immunol. 2000;12(2):139–147. doi: 10.1006/smim.2000.0216.
  • Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol. 2001;19(1):197–223. doi: 10.1146/annurev.immunol.19.1.197.
  • Lanier LL. On guard—activating NK cell receptors. Nat Immunol. 2001;2(1):23–27. doi: 10.1038/83130.
  • Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331(6013):44–49. doi: 10.1126/science.1198687.
  • Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, Tyan D, Lanier LL, Parham P. Human diversity in killer cell inhibitory receptor genes. Immunity. 1997;7(6):753–763. doi: 10.1016/s1074-7613(00)80394-5.
  • Trowsdale J, Barten R, Haude A, Stewart CA, Beck S, Wilson MJ. The genomic context of natural killer receptor extended gene families. Immunol Rev. 2001;181(1):20–38. doi: 10.1034/j.1600-065x.2001.1810102.x.
  • Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20(1):217–251. doi: 10.1146/annurev.immunol.20.092501.134942.
  • Vitale M, Cantoni C, Della Chiesa M, Ferlazzo G, Carlomagno S, Pende D, Falco M, Pessino A, Muccio L, De Maria A. et al. An historical overview: the discovery of how NK cells can kill enemies, recruit defense troops, and more. Front Immunol. 2019;10:1415. doi: 10.3389/fimmu.2019.01415.
  • Bjorkstrom NK, Ljunggren HG, Michaelsson J. Emerging insights into natural killer cells in human peripheral tissues. Nat Rev Immunol. 2016;16(5):310–320. doi: 10.1038/nri.2016.34.
  • Freud AG, Mundy-Bosse BL, Yu J, Caligiuri MA. The broad spectrum of human natural killer cell diversity. Immunity. 2017;47(5):820–833. doi: 10.1016/j.immuni.2017.10.008.
  • Ochoa MC, Minute L, Rodriguez I, Garasa S, Perez‐Ruiz E, Inogés S, Melero I, Berraondo P. Antibody-dependent cell cytotoxicity: immunotherapy strategies enhancing effector NK cells. Immunol Cell Biol. 2017;95(4):347–355. doi: 10.1038/icb.2017.6.
  • Cerwenka A, Lanier LL. Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol. 2016;16(2):112–123. doi: 10.1038/nri.2015.9.
  • Lopez-Botet M, De Maria A, Muntasell A, Della Chiesa M, Vilches C. Adaptive NK cell response to human cytomegalovirus: Facts and open issues. Semin Immunol. 2023;65:101706. doi: 10.1016/j.smim.2022.101706.
  • Tang F, Li J, Qi L, Liu D, Bo Y, Qin S, Miao Y, Yu K, Hou W, Li J. et al. A pan-cancer single-cell panorama of human natural killer cells. Cell. 2023;186(19):4235–4251 e4220. doi: 10.1016/j.cell.2023.07.034.
  • Anfossi N, André P, Guia S, Falk CS, Roetynck S, Stewart CA, Breso V, Frassati C, Reviron D, Middleton D. et al. Human NK cell education by inhibitory receptors for MHC class I. Immunity. 2006;25(2):331–342. doi: 10.1016/j.immuni.2006.06.013.
  • Orr MT, Lanier LL. Natural killer cell education and tolerance. Cell. 2010;142(6):847–856. doi: 10.1016/j.cell.2010.08.031.
  • Boudreau JE, Hsu KC. Natural killer cell education in human health and disease. Curr Opin Immunol. 2018;50:102–111. doi: 10.1016/j.coi.2017.11.003.
  • Vitale M, Cantoni C, Pietra G, Mingari MC, Moretta L. Effect of tumor cells and tumor microenvironment on NK-cell function. Eur J Immunol. 2014;44(6):1582–1592. doi: 10.1002/eji.201344272.
  • Anderson NM, Simon MC. The tumor microenvironment. Curr Biol. 2020;30(16):R921–R925. doi: 10.1016/j.cub.2020.06.081.
  • Balzasch BM, Cerwenka A. Microenvironmental signals shaping NK-cell reactivity in cancer. Eur J Immunol. 2023;53(12):e2250103. doi: 10.1002/eji.202250103.
  • de Visser KE, Joyce JA. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell. 2023;41(3):374–403. doi: 10.1016/j.ccell.2023.02.016.
  • Castriconi R, Carrega P, Dondero A, Bellora F, Casu B, Regis S, Ferlazzo G, Bottino C. Molecular mechanisms directing migration and retention of natural killer cells in human tissues. Front Immunol. 2018;9:2324. doi: 10.3389/fimmu.2018.02324.
  • Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–640. doi: 10.1016/s1471-4906(01)02060-9.
  • Caligiuri MA. Human natural killer cells. Blood. 2008;112(3):461–469. doi: 10.1182/blood-2007-09-077438.
  • Burke S, Lakshmikanth T, Colucci F, Carbone E. New views on natural killer cell-based immunotherapy for melanoma treatment. Trends Immunol. 2010;31(9):339–345. doi: 10.1016/j.it.2010.06.003.
  • Lavergne E, Combadière B, Bonduelle O, Iga M, Gao J-L, Maho M, Boissonnas A, Murphy PM, Debré P, Combadière C. Fractalkine mediates natural killer-dependent antitumor responses in vivo. Cancer Res. 2003;63(21):7468–7474.
  • Tsuchiyama T, Nakamoto Y, Sakai Y, Marukawa Y, Kitahara M, Mukaida N, Kaneko S. Prolonged, NK cell-mediated antitumor effects of suicide gene therapy combined with monocyte chemoattractant protein-1 against hepatocellular carcinoma. J Immunol. 2007;178(1):574–583. doi: 10.4049/jimmunol.178.1.574.
  • Mamessier E, Sylvain A, Thibult M-L, Houvenaeghel G, Jacquemier J, Castellano R, Gonçalves A, André P, Romagné F, Thibault G. et al. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest. 2011;121(9):3609–3622. doi: 10.1172/JCI45816.
  • Carrega P, Bonaccorsi I, Di Carlo E, Morandi B, Paul P, Rizzello V, Cipollone G, Navarra G, Mingari MC, Moretta L. et al. CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph. J Immunol. 2014;192(8):3805–3815. doi: 10.4049/jimmunol.1301889.
  • Portale F, Di Mitri D. NK cells in cancer: mechanisms of dysfunction and therapeutic potential. Int J Mol Sci. 2023;24(11):9521. doi: 10.3390/ijms24119521.
  • Halama N, Braun M, Kahlert C, Spille A, Quack C, Rahbari N, Koch M, Weitz J, Kloor M, Zoernig I. et al. Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines. Clin Cancer Res. 2011;17(4):678–689. doi: 10.1158/1078-0432.CCR-10-2173.
  • Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, André P, Dieu-Nosjean M-C, Alifano M, Régnard J-F. et al. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 2011;71(16):5412–5422. doi: 10.1158/0008-5472.CAN-10-4179.
  • Ali TH, Pisanti S, Ciaglia E, Mortarini R, Anichini A, Garofalo C, Tallerico R, Santinami M, Gulletta E, Ietto C. et al. Enrichment of CD56(dim)KIR + CD57 + highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients. Nat Commun. 2014;5(1):5639. doi: 10.1038/ncomms6639.
  • Pachynski RK, Zabel BA, Kohrt HE, Tejeda NM, Monnier J, Swanson CD, Holzer AK, Gentles AJ, Sperinde GV, Edalati A. et al. The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses. J Exp Med. 2012;209(8):1427–1435. doi: 10.1084/jem.20112124.
  • Parodi M, Pedrazzi M, Cantoni C, Averna M, Patrone M, Cavaletto M, Spertino S, Pende D, Balsamo M, Pietra G. et al. Natural killer (Nk)/melanoma cell interaction induces NK-mediated release of chemotactic High Mobility Group Box-1 (HMGB1) capable of amplifying NK cell recruitment. Oncoimmunology. 2015;4(12):e1052353. doi: 10.1080/2162402X.2015.1052353.
  • Bottcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, Reis e Sousa C. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell. 2018;172(5):1022–1037 e1014. doi: 10.1016/j.cell.2018.01.004.
  • Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M, Combes AJ, Nelson AE, Loo K, Kumar R, Rosenblum MD. et al. A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments. Nat Med. 2018;24(8):1178–1191. doi: 10.1038/s41591-018-0085-8.
  • Castriconi R, Dondero A, Bellora F, Moretta L, Castellano A, Locatelli F, Corrias MV, Moretta A, Bottino C. Neuroblastoma-derived TGF-β1 modulates the chemokine receptor repertoire of human resting NK cells. J Immunol. 2013;190(10):5321–5328. doi: 10.4049/jimmunol.1202693.
  • Balkwill FR, Mantovani A. Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol. 2012;22(1):33–40. doi: 10.1016/j.semcancer.2011.12.005.
  • Labani-Motlagh A, Ashja-Mahdavi M, Loskog A. The tumor microenvironment: a milieu hindering and obstructing antitumor immune responses. Front Immunol. 2020;11:940. doi: 10.3389/fimmu.2020.00940.
  • Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12(4):253–268. doi: 10.1038/nri3175.
  • Bonavita E, Galdiero MR, Jaillon S, Mantovani A. Phagocytes as corrupted policemen in cancer-related Inflammation. Adv Cancer Res. 2015;128:141–171. doi: 10.1016/bs.acr.2015.04.013.
  • Hedrick CC, Malanchi I. Neutrophils in cancer: heterogeneous and multifaceted. Nat Rev Immunol. 2022;22(3):173–187. doi: 10.1038/s41577-021-00571-6.
  • Tumino N, Besi F, Martini S, Di Pace AL, Munari E, Quatrini L, Pelosi A, Fiore PF, Fiscon G, Paci P. et al. Polymorphonuclear myeloid-derived suppressor cells are abundant in peripheral blood of cancer patients and suppress natural killer cell anti-tumor activity. Front Immunol. 2022;12:803014. doi: 10.3389/fimmu.2021.803014.
  • Sun R, Xiong Y, Liu H, Gao C, Su L, Weng J, Yuan X, Zhang D, Feng J. Tumor-associated neutrophils suppress antitumor immunity of NK cells through the PD-L1/PD-1 axis. Transl Oncol. 2020;13(10):100825. doi: 10.1016/j.tranon.2020.100825.
  • Ghiringhelli F, Ménard C, Terme M, Flament C, Taieb J, Chaput N, Puig PE, Novault S, Escudier B, Vivier E. et al. CD4 + CD25 + regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner. J Exp Med. 2005;202(8):1075–1085. doi: 10.1084/jem.20051511.
  • Brownlie D, Scharenberg M, Mold JE, Hård J, Kekäläinen E, Buggert M, Nguyen S, Wilson JN, Al-Ameri M, Ljunggren H-G. et al. Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood. Proc Natl Acad Sci USA. 2021;118(11). doi: 10.1073/pnas.2016580118.
  • Rennert C, Tauber C, Fehrenbach P, Heim K, Bettinger D, Sogukpinar Ö, Schuch A, Zecher BF, Bengsch B, Lang SA. et al. Adaptive subsets limit the anti-tumoral NK-Cell activity in hepatocellular carcinoma. Cells. 2021;10(6):1369. doi: 10.3390/cells10061369.
  • An Y, Liu F, Chen Y, Yang Q. Crosstalk between cancer-associated fibroblasts and immune cells in cancer. J Cell Mol Med. 2020;24(1):13–24. doi: 10.1111/jcmm.14745.
  • Lavie D, Ben-Shmuel A, Erez N, Scherz-Shouval R. Cancer-associated fibroblasts in the single-cell era. Nat Cancer. 2022;3(7):793–807. doi: 10.1038/s43018-022-00411-z.
  • Balsamo M, Scordamaglia F, Pietra G, Manzini C, Cantoni C, Boitano M, Queirolo P, Vermi W, Facchetti F, Moretta A. et al. Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity. Proc Natl Acad Sci USA. 2009;106(49):20847–20852. doi: 10.1073/pnas.0906481106.
  • Li T, Yang Y, Hua X, Wang G, Liu W, Jia C, Tai Y, Zhang Q, Chen G. Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO. Cancer Lett. 2012;318(2):154–161. doi: 10.1016/j.canlet.2011.12.020.
  • Li T, Yi S, Liu W, Jia C, Wang G, Hua X, Tai Y, Zhang Q, Chen G. Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity. Med Oncol. 2013;30(3):663. doi: 10.1007/s12032-013-0663-z.
  • Vasold J, Wagner M, Drolle H, Deniffel C, Kütt A, Oostendorp R, Sironi S, Rieger C, Fiegl M. The bone marrow microenvironment is a critical player in the NK cell response against acute myeloid leukaemia in vitro. Leuk Res. 2015;39(2):257–262. doi: 10.1016/j.leukres.2014.12.001.
  • Shi M, Zhu J, Wang R, Chen X, Mi L, Walz T, Springer TA. Latent TGF-β structure and activation. Nature. 2011;474(7351):343–349. doi: 10.1038/nature10152.
  • Travis MA, Sheppard D. TGF-β Activation and Function in Immunity. Annu Rev Immunol. 2014;32(1):51–82. doi: 10.1146/annurev-immunol-032713-120257.
  • Pietra G, Manzini C, Rivara S, Vitale M, Cantoni C, Petretto A, Balsamo M, Conte R, Benelli R, Minghelli S. et al. Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res. 2012;72(6):1407–1415. doi: 10.1158/0008-5472.CAN-11-2544.
  • Hoskin DW, Mader JS, Furlong SJ, Conrad DM, Blay J. Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review). Int J Oncol. 2008;32:527–535. doi: 10.3892/ijo.32.3.527.
  • Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E, Conte R, Biassoni R, Bottino C, Moretta L, Moretta A. Transforming growth factor β1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA. 2003;100(7):4120–4125. doi: 10.1073/pnas.0730640100.
  • Marcenaro E, Chiesa MD, Bellora F, Parolini S, Millo R, Moretta L, Moretta A. IL-12 or IL-4 prime human NK cells to mediate functionally divergent interactions with dendritic cells or tumors. J Immunol. 2005;174(7):3992–3998. doi: 10.4049/jimmunol.174.7.3992.
  • Krockenberger M, Dombrowski Y, Weidler C, Ossadnik M, Hönig A, Häusler S, Voigt H, Becker JC, Leng L, Steinle A. et al. Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. J Immunol. 2008;180(11):7338–7348. doi: 10.4049/jimmunol.180.11.7338.
  • Gubbels JA, Felder M, Horibata S, Belisle JA, Kapur A, Holden H, Petrie S, Migneault M, Rancourt C, Connor JP. et al. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells. Mol Cancer. 2010;9(1):11. doi: 10.1186/1476-4598-9-11.
  • Crane CA, Han SJ, Barry JJ, Ahn BJ, Lanier LL, Parsa AT. TGF- downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients. Neuro Oncol. 2010;12(1):7–13. doi: 10.1093/neuonc/nop009.
  • Hilpert J, Grosse-Hovest L, Grünebach F, Buechele C, Nuebling T, Raum T, Steinle A, Salih HR. Comprehensive analysis of NKG2D ligand expression and release in leukemia: implications for NKG2D-mediated NK cell responses. J Immunol. 2012;189(3):1360–1371. doi: 10.4049/jimmunol.1200796.
  • Gill S, Vasey AE, De Souza A, Baker J, Smith AT, Kohrt HE, Florek M, Gibbs KD, Tate K, Ritchie DS. et al. Rapid development of exhaustion and down-regulation of eomesodermin limit the antitumor activity of adoptively transferred murine natural killer cells. Blood. 2012;119(24):5758–5768. doi: 10.1182/blood-2012-03-415364.
  • Ben-Shmuel A, Biber G, Barda-Saad M. Unleashing natural killer cells in the tumor microenvironment-the next generation of immunotherapy? Front Immunol. 2020;11:275. doi: 10.3389/fimmu.2020.00275.
  • O’Brien KL, Finlay DK. Immunometabolism and natural killer cell responses. Nat Rev Immunol. 2019;19(5):282–290. doi: 10.1038/s41577-019-0139-2.
  • Yang Y, Chen L, Zheng B, Zhou S. Metabolic hallmarks of natural killer cells in the tumor microenvironment and implications in cancer immunotherapy. Oncogene. 2023;42(1):1–10. doi: 10.1038/s41388-022-02562-w.
  • Cong J, Wang X, Zheng X, Wang D, Fu B, Sun R, Tian Z, Wei H. Dysfunction of natural killer cells by FBP1-induced inhibition of glycolysis during lung cancer progression. Cell Metab. 2018;28(2):243–255 e245. doi: 10.1016/j.cmet.2018.06.021.
  • Benson DM Jr., Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, Baiocchi RA, Zhang J, Yu J, Smith MK. et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibody. Blood. 2010;116(13):2286–2294. doi: 10.1182/blood-2010-02-271874.
  • MacFarlane AWT, Jillab M, Plimack ER, Hudes GR, Uzzo RG, Litwin S, Dulaimi E, Al-Saleem T, Campbell KS. PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection. Cancer Immunol Res. 2014;2(4):320–331. doi: 10.1158/2326-6066.CIR-13-0133.
  • da Silva IP, Gallois A, Jimenez-Baranda S, Khan S, Anderson AC, Kuchroo VK, Osman I, Bhardwaj N. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res. 2014;2(5):410–422. doi: 10.1158/2326-6066.CIR-13-0171.
  • Pesce S, Greppi M, Tabellini G, Rampinelli F, Parolini S, Olive D, Moretta L, Moretta A, Marcenaro E. Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization. J Allergy Clin Immunol. 2017;139(1):335–346 e333. doi: 10.1016/j.jaci.2016.04.025.
  • Zhang Q, Bi J, Zheng X, Chen Y, Wang H, Wu W, Wang Z, Wu Q, Peng H, Wei H. et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat Immunol. 2018;19(7):723–732. doi: 10.1038/s41590-018-0132-0.
  • Khan M, Arooj S, Wang H. NK cell-based immune checkpoint Inhibition. Front Immunol. 2020;11:167. doi: 10.3389/fimmu.2020.00167.
  • Alteber Z, Kotturi MF, Whelan S, Ganguly S, Weyl E, Pardoll DM, Hunter J, Ophir E. Therapeutic targeting of checkpoint receptors within the dnam1 axis. Cancer Discov. 2021;11(5):1040–1051. doi: 10.1158/2159-8290.CD-20-1248.
  • Jia H, Yang H, Xiong H, Luo KQ. NK cell exhaustion in the tumor microenvironment. Front Immunol. 2023;14:1303605. doi: 10.3389/fimmu.2023.1303605.
  • Wang Y, Chu J, Yi P, Dong W, Saultz J, Wang Y, Wang H, Scoville S, Zhang J, Wu L-C. et al. SMAD4 promotes TGF-β–independent NK cell homeostasis and maturation and antitumor immunity. J Clin Invest. 2018;128(11):5123–5136. doi: 10.1172/JCI121227.
  • Xu D, Han Q, Hou Z, Zhang C, Zhang J. miR-146a negatively regulates NK cell functions via STAT1 signaling. Cell Mol Immunol. 2017;14:712–720. doi: 10.1038/cmi.2015.113.
  • Pan C, Xiang L, Pan Z, Wang X, Li J, Zhuge L, Fang P, Xie Q, Hu X. MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer. Cancer Cell Int. 2018;18(1). doi: 10.1186/s12935-018-0542-y.
  • Della Chiesa M, Carlomagno S, Frumento G, Balsamo M, Cantoni C, Conte R, Moretta L, Moretta A, Vitale M. The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood. 2006;108(13):4118–4125. doi: 10.1182/blood-2006-03-006700.
  • Wilson EB, El-Jawhari JJ, Neilson AL, Hall GD, Melcher AA, Meade JL, Cook GP. Human tumour immune evasion via TGF-β blocks NK cell activation but not survival allowing therapeutic restoration of anti-tumour activity. PLOS ONE. 2011;6(9):e22842. doi: 10.1371/journal.pone.0022842.
  • Balsamo M, Manzini C, Pietra G, Raggi F, Blengio F, Mingari MC, Varesio L, Moretta L, Bosco MC, Vitale M. et al. Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC. Eur J Immunol. 2013;43(10):2756–2764. doi: 10.1002/eji.201343448.
  • Hasmim M, Messai Y, Ziani L, Thiery J, Bouhris J-H, Noman MZ, Chouaib S. Critical role of tumor microenvironment in shaping NK Cell Functions: implication of hypoxic stress. Front Immunol. 2015;6:482. doi: 10.3389/fimmu.2015.00482.
  • Ni J, Wang X, Stojanovic A, Zhang Q, Wincher M, Bühler L, Arnold A, Correia MP, Winkler M, Koch P-S. et al. Single-cell RNA sequencing of tumor-infiltrating nk cells reveals that inhibition of transcription factor HIF-1α unleashes NK cell activity. Immunity. 2020;52(6):1075–1087 e1078. doi: 10.1016/j.immuni.2020.05.001.
  • Huergo-Zapico L, Parodi M, Cantoni C, Lavarello C, Fernández-Martínez JL, Petretto A, DeAndrés-Galiana EJ, Balsamo M, López-Soto A, Pietra G. et al. NK-cell editing mediates epithelial-to-mesenchymal transition via phenotypic and proteomic changes in melanoma cell lines. Cancer Res. 2018;78(14):3913–3925. doi: 10.1158/0008-5472.CAN-17-1891.
  • Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 2002;419(6908):734–738. doi: 10.1038/nature01112.
  • Molfetta R, Quatrini L, Zitti B, Capuano C, Galandrini R, Santoni A, Paolini R. Regulation of NKG2D expression and signaling by endocytosis. Trends Immunol. 2016;37(11):790–802. doi: 10.1016/j.it.2016.08.015.
  • Costello RT, Sivori S, Marcenaro E, Lafage-Pochitaloff M, Mozziconacci M-J, Reviron D, Gastaut J-A, Pende D, Olive D, Moretta A. Defective expression and function of natural killer cell–triggering receptors in patients with acute myeloid leukemia. Blood. 2002;99(10):3661–3667. doi: 10.1182/blood.v99.10.3661.
  • Garcia-Iglesias T, Del Toro-Arreola A, Albarran-Somoza B, Del Toro-Arreola S, Sanchez-Hernandez PE, Ramirez- DueñDueñAs MG, Balderas-Peña LMA, Bravo-Cuellar A, Ortiz-Lazareno PC, Daneri-Navarro A. et al. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC Cancer. 2009;9(1):186. doi: 10.1186/1471-2407-9-186.
  • Carlsten M, Norell H, Bryceson YT, Poschke I, Schedvins K, Ljunggren H-G, Kiessling R, Malmberg K-J. Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J Immunol. 2009;183(8):4921–4930. doi: 10.4049/jimmunol.0901226.
  • Sanchez-Correa B, Gayoso I, Bergua JM, Casado JG, Morgado S, Solana R, Tarazona R. Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients. Immunol Cell Biol. 2012;90(1):109–115. doi: 10.1038/icb.2011.15.
  • Pesce S, Tabellini G, Cantoni C, Patrizi O, Coltrini D, Rampinelli F, Matta J, Vivier E, Moretta A, Parolini S. et al. B7-H6-mediated downregulation of NKp30 in NK cells contributes to ovarian carcinoma immune escape. Oncoimmunology. 2015;4(4):e1001224. doi: 10.1080/2162402X.2014.1001224.
  • Xu Z, Zhang T, Zhuang R, Zhang Y, Jia W, Song C, Yang K, Yang A, Jin B. Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients. BMC Immunol. 2009;10(1):34. doi: 10.1186/1471-2172-10-34.
  • Peruzzi G, Femnou L, Gil-Krzewska A, Borrego F, Weck J, Krzewski K, Coligan JE. Membrane-type 6 matrix metalloproteinase regulates the activation-induced downmodulation of CD16 in human primary NK cells. J Immunol. 2013;191(4):1883–1894. doi: 10.4049/jimmunol.1300313.
  • Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, Luo X, Cooley S, Verneris M, Walcheck B. et al. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood. 2013;121(18):3599–3608. doi: 10.1182/blood-2012-04-425397.
  • Lanier LL. NKG2D receptor and its ligands in host defense. Cancer Immunol Res. 2015;3(6):575–582. doi: 10.1158/2326-6066.CIR-15-0098.
  • Kanaya M, Shibuya K, Hirochika R, Kanemoto M, Ohashi K, Okada M, Wagatsuma Y, Cho Y, Kojima H, Teshima T. et al. Soluble DNAM-1, as a predictive biomarker for acute graft-versus-host disease. PLOS ONE. 2016;11(6):e0154173. doi: 10.1371/journal.pone.0154173.
  • Molfetta R, Milito ND, Zitti B, Lecce M, Fionda C, Cippitelli M, Santoni A, Paolini R. The Ubiquitin-proteasome pathway regulates Nectin2/CD112 expression and impairs NK cell recognition and killing. Eur J Immunol. 2019;49(6):873–883. doi: 10.1002/eji.201847848.
  • Zhou Q, Gil-Krzewska A, Peruzzi G, Borrego F. Matrix metalloproteinases inhibition promotes the polyfunctionality of human natural killer cells in therapeutic antibody-based anti-tumour immunotherapy. Clin Exp Immunol. 2013;173(1):131–139. doi: 10.1111/cei.12095.
  • Pham DH, Kim, J.S., Kim, S.K., Shin, D.J., Hyun, H., Yoon, M.S., Kang, S.J., Ryu, Y.J., Cho, J.S., Yoon, J.H., Lee, J.S. Effects of ADAM10 and ADAM17 inhibitors on natural killer cell expansion and antibody-dependent cellular cytotoxicity against breast cancer cells in vitro. Anticancer Res. 2017;37:5507–5513. doi: 10.21873/anticanres.11981.
  • Srpan K, Ambrose A, Karampatzakis A, Saeed M, Cartwright ANR, Guldevall K, De Matos GDSC, Önfelt B, Davis DM. Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells. J Cell Biol. 2018;217(9):3267–3283. doi: 10.1083/jcb.201712085.
  • Rocca YS, Roberti MP, Arriaga JM, Amat M, Bruno L, Pampena MB, Huertas E, Loria FS, Pairola A, Bianchini M. et al. Altered phenotype in peripheral blood and tumor-associated NK cells from colorectal cancer patients. Innate Immun. 2013;19(1):76–85. doi: 10.1177/1753425912453187.
  • Fauriat C, Just-Landi S, Mallet F, Arnoulet C, Sainty D, Olive D, Costello RT. Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood. 2007;109(1):323–330. doi: 10.1182/blood-2005-08-027979.
  • Han B, Mao F-Y, Zhao Y-L, Lv Y-P, Teng Y-S, Duan M, Chen W, Cheng P, Wang T-T, Liang Z-Y. et al. Altered NKp30, NKp46, NKG2D, and DNAM-1 expression on circulating nk cells is associated with tumor progression in human gastric cancer. J Immunol Res. 2018;2018:1–9. doi: 10.1155/2018/6248590.
  • Dougall WC, Kurtulus S, Smyth MJ, Anderson AC. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol Rev. 2017;276(1):112–120. doi: 10.1111/imr.12518.
  • Castriconi R, Dondero A, Augugliaro R, Cantoni C, Carnemolla B, Sementa AR, Negri F, Conte R, Corrias MV, Moretta L. et al. Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis. Proc Natl Acad Sci USA. 2004;101(34):12640–12645. doi: 10.1073/pnas.0405025101.
  • Malmberg KJ, Levitsky V, Norell H, Matos CTD, Carlsten M, Schedvins K, Rabbani H, Moretta A, Söderström K, Levitskaya J. et al. IFN-γ protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism. J Clin Invest. 2002;110(10):1515–1523. doi: 10.1172/JCI15564.
  • Balsamo M, Vermi W, Parodi M, Pietra G, Manzini C, Queirolo P, Lonardi S, Augugliaro R, Moretta A, Facchetti F. et al. Melanoma cells become resistant to NK-cell-mediated killing when exposed to NK-cell numbers compatible with NK-cell infiltration in the tumor. Eur J Immunol. 2012;42(7):1833–1842. doi: 10.1002/eji.201142179.
  • Bellucci R, Martin A, Bommarito D, Wang K, Hansen SH, Freeman GJ, Ritz J. Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression. Oncoimmunology. 2015;4(6):e1008824. doi: 10.1080/2162402X.2015.1008824.
  • Raulet DH, Gasser S, Gowen BG, Deng W, Jung H. Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol. 2013;31(1):413–441. doi: 10.1146/annurev-immunol-032712-095951.
  • El-Gazzar A, Groh V, Spies T. Immunobiology and conflicting roles of the human NKG2D lymphocyte receptor and its ligands in cancer. J Immunol. 2013;191(4):1509–1515. doi: 10.4049/jimmunol.1301071.
  • Ferrari de Andrade L, Tay RE, Pan D, Luoma AM, Ito Y, Badrinath S, Tsoucas D, Franz B, May KF, Harvey CJ. et al. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity. Science. 2018;359(6383):1537–1542. doi: 10.1126/science.aao0505.
  • Waldhauer I, Steinle A. Proteolytic release of soluble UL16-binding protein 2 from tumor cells. Cancer Res. 2006;66(5):2520–2526. doi: 10.1158/0008-5472.CAN-05-2520.
  • Fuertes MB, Girart MV, Molinero LL, Domaica CI, Rossi LE, Barrio MM, Mordoh J, Rabinovich GA, Zwirner NW. Intracellular retention of the NKG2D ligand MHC class I chain-related gene a in human melanomas confers immune privilege and prevents NK cell-mediated cytotoxicity. J Immunol. 2008;180(7):4606–4614. doi: 10.4049/jimmunol.180.7.4606.
  • Waldhauer I, Goehlsdorf D, Gieseke F, Weinschenk T, Wittenbrink M, Ludwig A, Stevanovic S, Rammensee H-G, Steinle A. Tumor-associated MICA is shed by ADAM proteases. Cancer Res. 2008;68(15):6368–6376. doi: 10.1158/0008-5472.CAN-07-6768.
  • Fernandez-Messina L, Reyburn HT, Vales-Gomez M. A short half-life of ULBP1 at the cell surface due to internalization and proteosomal degradation. Immunol Cell Biol. 2016;94(5):479–485. doi: 10.1038/icb.2016.2.
  • Labani-Motlagh A, Israelsson P, Ottander U, Lundin E, Nagaev I, Nagaeva O, Dehlin E, Baranov V, Mincheva-Nilsson L. Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumour Biol. 2016;37(4):5455–5466. doi: 10.1007/s13277-015-4313-2.
  • Stern-Ginossar N, Gur C, Biton M, Horwitz E, Elboim M, Stanietsky N, Mandelboim M, Mandelboim O. Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D. Nat Immunol. 2008;9(9):1065–1073. doi: 10.1038/ni.1642.
  • Xie J, Liu M, Li Y, Nie Y, Mi Q, Zhao S. Ovarian tumor-associated microRNA-20a decreases natural killer cell cytotoxicity by downregulating MICA/B expression. Cell Mol Immunol. 2014;11(5):495–502. doi: 10.1038/cmi.2014.30.
  • Trinh TL, Kandell WM, Donatelli SS, Tu N, Tejera MM, Gilvary DL, Eksioglu EA, Burnette A, Adams WA, Liu J. et al. Immune evasion by TGFβ-induced miR-183 repression of MICA/B expression in human lung tumor cells. Oncoimmunology. 2019;8(4):e1557372. doi: 10.1080/2162402X.2018.1557372.
  • Al-Abdallah A, Jahanbani I, Mehdawi H, Ali RH, Al-Brahim N, Mojiminiyi O, Junaid TA. Down-regulation of the human major histocompatibility complex class I chain-related gene a (MICA) and its receptor is mediated by microRNA-146b-5p and is a potential mechanism of immunoediting in papillary thyroid carcinoma. Exp Mol Pathol. 2020;113:104379. doi: 10.1016/j.yexmp.2020.104379.
  • Pesce S, Greppi M, Ferretti E, Obino V, Carlomagno S, Rutigliani M, Thoren FB, Sivori S, Castagnola P, Candiani S. et al. miRNAs in NK cell-based immune responses and cancer immunotherapy. Front Cell Dev Biol. 2020;8:119. doi: 10.3389/fcell.2020.00119.
  • Baury B, Masson D, McDermott BM, Jarry A, Blottière HM, Blanchardie P, Laboisse CL, Lustenberger P, Racaniello VR, Denis MG. Identification of secreted CD155 isoforms. Biochem Biophys Res Commun. 2003;309(1):175–182. doi: 10.1016/s0006-291x(03)01560-2.
  • Zitti B, Molfetta R, Fionda C, Quatrini L, Stabile H, Lecce M, de Turris V, Ricciardi MR, Petrucci MT, Cippitelli M. et al. Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells. Sci Rep. 2017;7(1):10445. doi: 10.1038/s41598-017-10403-0.
  • Okumura G, Iguchi-Manaka A, Murata R, Yamashita-Kanemaru Y, Shibuya A, Shibuya K. Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells. J Exp Med. 2020;217(4):1. doi: 10.1084/jem.20191290.
  • Pogge von Strandmann E, Simhadri VR, von Tresckow B, Sasse S, Reiners K, Hansen HP, Rothe A, Böll B, Simhadri VL, Borchmann P. et al. Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity. 2007;27(6):965–974. doi: 10.1016/j.immuni.2007.10.010.
  • Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z, Fox B, Haldeman B, Ostrander CD, Kaifu T, Chabannon C. et al. The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med. 2009;206(7):1495–1503. doi: 10.1084/jem.20090681.
  • Reiners KS, Topolar D, Henke A, Simhadri VR, Kessler J, Sauer M, Bessler M, Hansen HP, Tawadros S, Herling M. et al. Soluble ligands for NK cell receptors promote evasion of chronic lymphocytic leukemia cells from NK cell anti-tumor activity. Blood. 2013;121(18):3658–3665. doi: 10.1182/blood-2013-01-476606.
  • Matta J, Baratin M, Chiche L, Forel J-M, Cognet C, Thomas G, Farnarier C, Piperoglou C, Papazian L, Chaussabel D. et al. Induction of B7-H6, a ligand for the natural killer cell–activating receptor NKp30, in inflammatory conditions. Blood. 2013;122(3):394–404. doi: 10.1182/blood-2013-01-481705.
  • Dassler-Plenker J, Reiners KS, van den Boorn JG, Hansen HP, Putschli B, Barnert S, Schuberth-Wagner C, Schubert R, Tüting T, Hallek M. et al. RIG-I activation induces the release of extracellular vesicles with antitumor activity. Oncoimmunology. 2016;5(10):e1219827. doi: 10.1080/2162402X.2016.1219827.
  • Schlecker E, Fiegler N, Arnold A, Altevogt P, Rose-John S, Moldenhauer G, Sucker A, Paschen A, von Strandmann EP, Textor S. et al. Metalloprotease-mediated tumor cell shedding of B7-H6, the ligand of the natural killer cell–activating receptor NKp30. Cancer Res. 2014;74(13):3429–3440. doi: 10.1158/0008-5472.CAN-13-3017.
  • Rosental B, Brusilovsky M, Hadad U, Oz D, Appel MY, Afergan F, Yossef R, Rosenberg LA, Aharoni A, Cerwenka A. et al. Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44. J Immunol. 2011;187(11):5693–5702. doi: 10.4049/jimmunol.1102267.
  • Gaggero S, Bruschi M, Petretto A, Parodi M, Zotto GD, Lavarello C, Prato C, Santucci L, Barbuto A, Bottino C. et al. Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor. Oncoimmunology. 2018;7(9):e1470730. doi: 10.1080/2162402X.2018.1470730.
  • Iguchi-Manaka A, Okumura G, Kojima H, Cho Y, Hirochika R, Bando H, Sato T, Yoshikawa H, Hara H, Shibuya A. et al. Increased soluble CD155 in the serum of cancer patients. PLOS ONE. 2016;11(4):e0152982. doi: 10.1371/journal.pone.0152982.
  • Willumsen N, Bager CL, Leeming DJ, Bay-Jensen AC, Karsdal MA. Nidogen-1 degraded by cathepsin s can be quantified in serum and is associated with non–small cell lung cancer. Neoplasia. 2017;19(4):271–278. doi: 10.1016/j.neo.2017.01.008.
  • Xing S, Ferrari de Andrade L. NKG2D and MICA/B shedding: a ‘tag game’ between NK cells and malignant cells. Clin Transl Immunol. 2020;9(12):e1230. doi: 10.1002/cti2.1230.
  • Al Absi A, Wurzer H, Guerin C, Hoffmann C, Moreau F, Mao X, Brown-Clay J, Petrolli R, Casellas CP, Dieterle M. et al. Actin cytoskeleton remodeling drives breast cancer cell escape from natural killer–mediated cytotoxicity. Cancer Res. 2018;78(19):5631–5643. doi: 10.1158/0008-5472.CAN-18-0441.
  • Parodi M, Centonze G, Murianni F, Orecchia P, Andriani F, Roato I, Gardelli C, Balsamo M, Moro M, Taiè G. et al. Hybrid epithelial-mesenchymal status of lung cancer dictates metastatic success through differential interaction with NK cells. J Immunother Cancer. 2024;12(3):e007895. doi: 10.1136/jitc-2023-007895.
  • Fiore PF, Di Pace AL, Conti LA, Tumino N, Besi F, Scaglione S, Munari E, Moretta L, Vacca P. Different effects of NK cells and NK-derived soluble factors on cell lines derived from primary or metastatic pancreatic cancers. Cancer Immunol Immunother. 2023;72(6):1417–1428. doi: 10.1007/s00262-022-03340-z.
  • Vivier E, Rebuffet L, Narni-Mancinelli E, Cornen S, Igarashi RY, Fantin VR. Natural killer cell therapies. Nature. 2024;626(8000):727–736. doi: 10.1038/s41586-023-06945-1.
  • Sivori S, Pende D, Quatrini L, Pietra G, Della Chiesa M, Vacca P, Tumino N, Moretta F, Mingari MC, Locatelli F. et al. NK cells and ILCs in tumor immunotherapy. Mol Aspects Med. 2021;80:100870. doi: 10.1016/j.mam.2020.100870.
  • Ahmadzadeh M, Rosenberg SA. IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood. 2006;107(6):2409–2414. doi: 10.1182/blood-2005-06-2399.
  • Wei S, Kryczek I, Edwards RP, Zou L, Szeliga W, Banerjee M, Cost M, Cheng P, Chang A, Redman B. et al. Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res. 2007;67(15):7487–7494. doi: 10.1158/0008-5472.CAN-07-0565.
  • Mitra S, Leonard WJ. Biology of IL-2 and its therapeutic modulation: Mechanisms and strategies. J Leukoc Biol. 2018;103(4):643–655. doi: 10.1002/JLB.2RI0717-278R.
  • Law TM, Motzer, R.J., Mazumdar, M., Sell, K.W., Walther, P., O’Connell, M., Khan, A., Vlamis, V., Vogelzang, N.J., Bajorin, D.F. Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer. 1995;76:824–832. doi: 10.1002/1097-0142(19950901)76:5<824:aid-cncr2820760517>3.0.co;2-n.
  • Parkhurst MR, Riley JP, Dudley ME, Rosenberg SA. Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. Clin Cancer Res. 2011;17(19):6287–6297. doi: 10.1158/1078-0432.CCR-11-1347.
  • Levin AM, Bates DL, Ring AM, Krieg C, Lin JT, Su L, Moraga I, Raeber ME, Bowman GR, Novick P. et al. Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’. Nature. 2012;484(7395):529–533. doi: 10.1038/nature10975.
  • Merchant R, Galligan C, Munegowda MA, Pearce LB, Lloyd P, Smith P, Merchant F, To MD. Fine-tuned long-acting interleukin-2 superkine potentiates durable immune responses in mice and non-human primate. J Immunother Cancer. 2022;10(1):e003155. doi: 10.1136/jitc-2021-003155.
  • Wolf NK, Blaj C, Picton LK, Snyder G, Zhang L, Nicolai CJ, Ndubaku CO, McWhirter SM, Garcia KC, Raulet DH. Synergy of a STING agonist and an IL-2 superkine in cancer immunotherapy against MHC I–deficient and MHC I + tumors. Proc Natl Acad Sci USA. 2022;119(22):e2200568119. doi: 10.1073/pnas.2200568119.
  • Gaggero S, Martinez-Fabregas J, Cozzani A, Fyfe PK, Leprohon M, Yang J, Thomasen FE, Winkelmann H, Magnez R, Conti AG. et al. IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein. Sci Immunol. 2022;7(78):eade5686. doi: 10.1126/sciimmunol.ade5686.
  • Zhou Y, Husman T, Cen X, Tsao T, Brown J, Bajpai A, Li M, Zhou K, Yang L. Interleukin 15 in Cell-Based Cancer Immunotherapy. Int J Mol Sci. 2022;23(13):7311. doi: 10.3390/ijms23137311.
  • Ferlazzo G, Pack M, Thomas D, Paludan C, Schmid D, Strowig T, Bougras G, Muller WA, Moretta L, Münz C. Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci USA. 2004;101(47):16606–16611. doi: 10.1073/pnas.0407522101.
  • Anton OM, Peterson ME, Hollander MJ, Dorward DW, Arora G, Traba J, Rajagopalan S, Snapp EL, Garcia KC, Waldmann TA. et al. Trans -endocytosis of intact IL-15Rα–IL-15 complex from presenting cells into NK cells favors signaling for proliferation. Proc Natl Acad Sci USA. 2020;117(1):522–531. doi: 10.1073/pnas.1911678117.
  • Han KP, Zhu X, Liu B, Jeng E, Kong L, Yovandich JL, Vyas VV, Marcus WD, Chavaillaz P-A, Romero CA. et al. IL-15: IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine. 2011;56(3):804–810. doi: 10.1016/j.cyto.2011.09.028.
  • Felices M, Chu S, Kodal B, Bendzick L, Ryan C, Lenvik AJ, Boylan KLM, Wong HC, Skubitz APN, Miller JS. et al. IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. Gynecol Oncol. 2017;145(3):453–461. doi: 10.1016/j.ygyno.2017.02.028.
  • Van der Meer JMR, Maas RJA, Guldevall K, Klarenaar K, de Jonge PKJD, Evert JSHV, van der Waart AB, Cany J, Safrit JT, Lee JH. et al. IL-15 superagonist N-803 improves IFNγ production and killing of leukemia and ovarian cancer cells by CD34+ progenitor-derived NK cells. Cancer Immunol Immunother. 2021;70(5):1305–1321. doi: 10.1007/s00262-020-02749-8.
  • Berrien-Elliott MM, Becker-Hapak M, Cashen AF, Jacobs M, Wong P, Foster M, McClain E, Desai S, Pence P, Cooley S. et al. Systemic IL-15 promotes allogeneic cell rejection in patients treated with natural killer cell adoptive therapy. Blood. 2022;139(8):1177–1183. doi: 10.1182/blood.2021011532.
  • Pende D, Meazza R. N-803: a double-edged sword in haplo-NK therapy. Blood. 2022;139(8):1122–1124. doi: 10.1182/blood.2021014789.
  • Felices M, Lenvik AJ, McElmurry R, Chu S, Hinderlie P, Bendzick L, Geller MA, Tolar J, Blazar BR, Miller JS. et al. Continuous treatment with IL-15 exhausts human NK cells via a metabolic defect. JCI Insight. 2018;3(3). doi: 10.1172/jci.insight.96219.
  • Merino A, Zhang B, Dougherty P, Luo X, Wang J, Blazar BR, Miller JS, Cichocki F. Chronic stimulation drives human NK cell dysfunction and epigenetic reprograming. J Clin Invest. 2019;129(9):3770–3785. doi: 10.1172/JCI125916.
  • Zhou T, Damsky W, Weizman O-E, McGeary MK, Hartmann KP, Rosen CE, Fischer S, Jackson R, Flavell RA, Wang J. et al. IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature. 2020;583(7817):609–614. doi: 10.1038/s41586-020-2422-6.
  • Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM. Cytokine-induced memory-like natural killer cells. Proc Natl Acad Sci USA. 2009;106(6):1915–1919. doi: 10.1073/pnas.0813192106.
  • Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18–preactivated NK cells against established tumors. J Exp Med. 2012;209(13):2351–2365. doi: 10.1084/jem.20120944.
  • Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, Leong JW, Abdel-Latif S, Schneider SE, Willey S. et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med. 2016;8(357):357ra123. doi: 10.1126/scitranslmed.aaf2341.
  • Uppendahl LD, Felices M, Bendzick L, Ryan C, Kodal B, Hinderlie P, Boylan KLM, Skubitz APN, Miller JS, Geller MA. Cytokine-induced memory-like natural killer cells have enhanced function, proliferation, and in vivo expansion against ovarian cancer cells. Gynecol Oncol. 2019;153(1):149–157. doi: 10.1016/j.ygyno.2019.01.006.
  • Marin ND, Krasnick BA, Becker-Hapak M, Conant L, Goedegebuure SP, Berrien-Elliott MM, Robbins KJ, Foltz JA, Foster M, Wong P. et al. Memory-like differentiation enhances nk cell responses to melanoma. Clin Cancer Res. 2021;27(17):4859–4869. doi: 10.1158/1078-0432.CCR-21-0851.
  • Jacobs MT, Wong P, Zhou AY, Becker-Hapak M, Marin ND, Marsala L, Foster M, Foltz JA, Cubitt CC, Tran J. et al. Memory-like differentiation, tumor-targeting mabs, and chimeric antigen receptors enhance natural killer cell responses to head and neck cancer. Clin Cancer Res. 2023;29(20):4196–4208. doi: 10.1158/1078-0432.CCR-23-0156.
  • Berrien-Elliott MM, Cashen AF, Cubitt CC, Neal CC, Wong P, Wagner JA, Foster M, Schappe T, Desai S, McClain E. et al. Multidimensional analyses of donor memory-like nk cells reveal new associations with response after adoptive immunotherapy for leukemia. Cancer Discov. 2020;10(12):1854–1871. doi: 10.1158/2159-8290.CD-20-0312.
  • Berrien-Elliott MM, Foltz JA, Russler-Germain DA, Neal CC, Tran J, Gang M, Wong P, Fisk B, Cubitt CC, Marin ND. et al. Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Sci Transl Med. 2022;14(633):eabm1375. doi: 10.1126/scitranslmed.abm1375.
  • Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol. 2023;20(6):359–371. doi: 10.1038/s41571-023-00754-1.
  • Grigor EJM, Fergusson D, Kekre N, Montroy J, Atkins H, Seftel MD, Daugaard M, Presseau J, Thavorn K, Hutton B. et al. Risks and benefits of chimeric antigen receptor T-Cell (CAR-T) therapy in cancer: a systematic review and meta-analysis. Transfus Med Rev. 2019;33(2):98–110. doi: 10.1016/j.tmrv.2019.01.005.
  • Miao L, Zhang Z, Ren Z, Tang F, Li Y. Obstacles and Coping Strategies of CAR-T Cell Immunotherapy in Solid Tumors. Front Immunol. 2021;12:687822. doi: 10.3389/fimmu.2021.687822.
  • Rafei H, Daher M, Rezvani K. Chimeric antigen receptor (CAR) natural killer (NK)-cell therapy: leveraging the power of innate immunity. Br J Haematol. 2021;193(2):216–230. doi: 10.1111/bjh.17186.
  • Moscarelli J, Zahavi D, Maynard R, Weiner LM. The next generation of cellular immunotherapy: chimeric antigen receptor-natural killer cells. Transpl Cell Ther. 2022;28(10):650–656. doi: 10.1016/j.jtct.2022.06.025.
  • Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, Suttorp M, Seifried E, Ottmann OG, Bug G. et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15(12):1563–1570. doi: 10.1016/j.jcyt.2013.06.017.
  • Zhang C, Oberoi P, Oelsner S, Waldmann A, Lindner A, Tonn T, Wels WS. Chimeric antigen receptor-engineered nk-92 cells: an off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. Front Immunol. 2017;8:533. doi: 10.3389/fimmu.2017.00533.
  • Raftery MJ, Franzén AS, Pecher G. CAR NK Cells: The Future is Now. Annu Rev Cancer Biol. 2023;7(1):229–246. doi: 10.1146/annurev-cancerbio-061521-082320.
  • Imai C, Iwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood. 2005;106(1):376–383. doi: 10.1182/blood-2004-12-4797.
  • Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell STEM Cell. 2018;23(2):181–192 e185. doi: 10.1016/j.stem.2018.06.002.
  • Quintarelli C, Sivori S, Caruso S, Carlomagno S, Falco M, Boffa I, Orlando D, Guercio M, Abbaszadeh Z, Sinibaldi M. et al. Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia. Leukemia. 2020;34(4):1102–1115. doi: 10.1038/s41375-019-0613-7.
  • Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M. et al. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020;382(6):545–553. doi: 10.1056/NEJMoa1910607.
  • Gang M, Marin ND, Wong P, Neal CC, Marsala L, Foster M, Schappe T, Meng W, Tran J, Schaettler M. et al. CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas. Blood. 2020;136(20):2308–2318. doi: 10.1182/blood.2020006619.
  • Marin D, Li Y, Basar R, Rafei H, Daher M, Dou J, Mohanty V, Dede M, Nieto Y, Uprety N. et al. Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19(+) B cell tumors: a phase 1/2 trial. Nat Med. 2024;30(3):772–784. doi: 10.1038/s41591-023-02785-8.
  • Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee H-G, Steinle A. Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood. 2003;102(4):1389–1396. doi: 10.1182/blood-2003-01-0019.
  • Carbone E, Neri, P., Mesuraca, M., Fulciniti, M.T., Otsuki, T., Pende, D., Groh, V., Spies, T., Pollio, G., Cosman, D., Catalano, L. HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood. 2005;105(1):251–258. doi: 10.1182/blood-2004-04-1422.
  • von Lilienfeld-Toal M, Frank S, Leyendecker C, Feyler S, Jarmin S, Morgan R, Glasmacher A, Märten A, Schmidt-Wolf IGH, Brossart P. et al. Reduced immune effector cell NKG2D expression and increased levels of soluble NKG2D ligands in multiple myeloma may not be causally linked. Cancer Immunol Immunother. 2010;59(6):829–839. doi: 10.1007/s00262-009-0807-3.
  • Mastaglio S, Wong E, Perera T, Ripley J, Blombery P, Smyth MJ, Koldej R, Ritchie D. Natural killer receptor ligand expression on acute myeloid leukemia impacts survival and relapse after chemotherapy. Blood Adv. 2018;2(4):335–346. doi: 10.1182/bloodadvances.2017015230.
  • Vago L, Gojo I. Immune escape and immunotherapy of acute myeloid leukemia. J Clin Invest. 2020;130(4):1552–1564. doi: 10.1172/JCI129204.
  • Sanchez-Correa B, Lopez-Sejas N, Duran E, Labella F, Alonso C, Solana R, Tarazona R. Modulation of NK cells with checkpoint inhibitors in the context of cancer immunotherapy. Cancer Immunol Immunother. 2019;68(5):861–870. doi: 10.1007/s00262-019-02336-6.
  • Allison M, Mathews J, Gilliland T, Mathew SO. Natural Killer Cell-Mediated Immunotherapy for Leukemia. Cancers (Basel). 2022;14(3):843. doi: 10.3390/cancers14030843.
  • Khaznadar Z, Boissel N, Agaugué S, Henry G, Cheok M, Vignon M, Geromin D, Cayuela J-M, Castaigne S, Pautas C. et al. Defective NK cells in acute myeloid leukemia patients at diagnosis are associated with blast transcriptional signatures of immune evasion. J Immunol. 2015;195(6):2580–2590. doi: 10.4049/jimmunol.1500262.
  • Minculescu L, Fischer-Nielsen A, Haastrup E, Ryder LP, Andersen NS, Schjoedt I, Friis LS, Kornblit BT, Petersen SL, Sengelov H. et al. Improved relapse-free survival in patients with high natural killer cell doses in grafts and during early immune reconstitution after allogeneic stem cell transplantation. Front Immunol. 2020;11:1068. doi: 10.3389/fimmu.2020.01068.
  • Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F. et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097–2100. doi: 10.1126/science.1068440.
  • Pende D, Marcenaro S, Falco M, Martini S, Bernardo ME, Montagna D, Romeo E, Cognet C, Martinetti M, Maccario R. et al. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood. 2009;113(13):3119–3129. doi: 10.1182/blood-2008-06-164103.
  • Moretta L, Locatelli F, Pende D, Marcenaro E, Mingari MC, Moretta A. Killer Ig–like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation. Blood. 2011;117(3):764–771. doi: 10.1182/blood-2010-08-264085.
  • Locatelli F, Pende D, Falco M, Della Chiesa M, Moretta A, Moretta L. NK cells mediate a crucial graft-versus-leukemia effect in haploidentical-HSCT to cure high-risk acute leukemia. Trends Immunol. 2018;39(7):577–590. doi: 10.1016/j.it.2018.04.009.
  • Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF. et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2008;14(6):641–650. doi: 10.1016/j.bbmt.2008.03.005.
  • Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco M, Handgretinger R, Moretta F. et al. HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders. Blood. 2014;124(5):822–826. doi: 10.1182/blood-2014-03-563817.
  • Oevermann L, Michaelis SU, Mezger M, Lang P, Toporski J, Bertaina A, Zecca M, Moretta L, Locatelli F, Handgretinger R. et al. KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL. Blood. 2014;124(17):2744–2747. doi: 10.1182/blood-2014-03-565069.
  • Merli P, Algeri M, Galaverna F, Bertaina V, Lucarelli B, Boccieri E, Becilli M, Quagliarella F, Rosignoli C, Biagini S. et al. TCRαβ/CD19 cell–depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis. Blood. 2024;143(3):279–289. doi: 10.1182/blood.2023021336.
  • Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, Marsh SGE, Geraghty D, Spellman S, Haagenson MD. et al. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood. 2010;116(14):2411–2419. doi: 10.1182/blood-2010-05-283051.
  • Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Marsh SGE, Spellman S, Haagenson MD, Saeturn K, Ladner M. et al. Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia. J Immunol. 2014;192(10):4592–4600. doi: 10.4049/jimmunol.1302517.
  • Weisdorf D, Cooley S, Wang T, Trachtenberg E, Vierra-Green C, Spellman S, Sees JA, Spahn A, Vogel J, Fehniger TA. et al. KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation. Blood Adv. 2020;4(4):740–754. doi: 10.1182/bloodadvances.2019001053.
  • Guethlein LA, Beyzaie N, Nemat-Gorgani N, Wang T, Ramesh V, Marin WM, Hollenbach JA, Schetelig J, Spellman SR, Marsh SGE. et al. Following transplantation for acute myelogenous leukemia, donor kir cen b02 better protects against relapse than KIR cen B01. J Immunol. 2021;206(12):3064–3072. doi: 10.4049/jimmunol.2100119.
  • Babor F, Peters C, Manser AR, Glogova E, Sauer M, Pötschger U, Ahlmann M, Cario G, Feuchtinger T, Gruhn B. et al. Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL. Bone Marrow Transpl. 2019;54(11):1847–1858. doi: 10.1038/s41409-019-0543-z.
  • Ciurea SO, Al Malki MM, Kongtim P, Fuchs EJ, Luznik L, Huang X-J, Ciceri F, Locatelli F, Aversa F, Castagna L. et al. The European society for blood and marrow transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation. Bone Marrow Transpl. 2020;55(1):12–24. doi: 10.1038/s41409-019-0499-z.
  • Little AM, Akbarzad‐Yousefi A, Anand A, Diaz Burlinson N, Dunn PPJ, Evseeva I, Latham K, Poulton K, Railton D, Vivers S. et al. BSHI guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation. Int J Immunogenet. 2021;48(2):75–109. doi: 10.1111/iji.12527.
  • Ciurea SO, Kongtim P, Soebbing D, Trikha P, Behbehani G, Rondon G, Olson A, Bashir Q, Gulbis AM, Indreshpal K. et al. Decrease post-transplant relapse using donor-derived expanded NK-cells. Leukemia. 2022;36(1):155–164. doi: 10.1038/s41375-021-01349-4.
  • Cascone T, Kar G, Spicer JD, García-Campelo R, Weder W, Daniel DB, Spigel DR, Hussein M, Mazieres J, Oliveira J. et al. Neoadjuvant durvalumab alone or combined with novel immuno-oncology agents in resectable lung cancer: the phase II NeoCOAST platform trial. Cancer Discov. 2023;13(11):2394–2411. doi: 10.1158/2159-8290.CD-23-0436.
  • Sukari A, Nagasaka M, Al-Hadidi A, Lum LG. Cancer immunology and immunotherapy. Anticancer Res. 2016;36(11):5593–5606. doi: 10.21873/anticanres.11144.
  • Brahmer JR, Govindan R, Anders RA, Antonia SJ, Sagorsky S, Davies MJ, Dubinett SM, Ferris A, Gandhi L, Garon EB. et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC). J Immunother Cancer. 2018;6(1):75. doi: 10.1186/s40425-018-0382-2.
  • Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB, Ahn M-J, Eder JP, Balmanoukian AS, Aggarwal C, Horn L. et al. Five-year overall survival for patients with advanced non‒small-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 Study. J Clin Oncol. 2019;37(28):2518–2527. doi: 10.1200/JCO.19.00934.
  • Marletta S, Fusco N, Munari E, Luchini C, Cimadamore A, Brunelli M, Querzoli G, Martini M, Vigliar E, Colombari R. et al. Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems. J Pers Med. 2022;12(7):1073. doi: 10.3390/jpm12071073.
  • Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, Wistuba II, Rimm DL, Tsao MS, Hirsch FR. et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021;18(6):345–362. doi: 10.1038/s41571-021-00473-5.
  • Torlakovic E, Lim HJ, Adam J, Barnes P, Bigras G, Chan AWH, Cheung CC, Chung J-H, Couture C, Fiset PO. et al. “Interchangeability” of PD-L1 immunohistochemistry assays: a meta-analysis of diagnostic accuracy. Mod Pathol. 2020;33(1):4–17. doi: 10.1038/s41379-019-0327-4.
  • Munari E, Rossi G, Zamboni G, Lunardi G, Marconi M, Sommaggio M, Netto GJ, Hoque MO, Brunelli M, Martignoni G. et al. PD-L1 Assays 22C3 and SP263 are not interchangeable in non–small cell lung cancer when considering clinically relevant cutoffs. Am J Surg Pathol. 2018;42(10):1384–1389. doi: 10.1097/PAS.0000000000001105.
  • Munari E, Querzoli G, Brunelli M, Marconi M, Sommaggio M, Cocchi MA, Martignoni G, Netto GJ, Caliò A, Quatrini L. et al. Comparison of three validated PD-L1 immunohistochemical assays in urothelial carcinoma of the bladder: interchangeability and issues related to patient selection. Front Immunol. 2022;13:954910. doi: 10.3389/fimmu.2022.954910.
  • Lu L, Zhan M, Li X-Y, Zhang H, Dauphars DJ, Jiang J, Yin H, Li S-Y, Luo S, Li Y. et al. Clinically approved combination immunotherapy: Current status, limitations, and future perspective. Curr Res Immunol. 2022;3:118–127. doi: 10.1016/j.crimmu.2022.05.003.
  • Walsh RJ, Sundar R, Lim JSJ. Immune checkpoint inhibitor combinations—current and emerging strategies. Br J Cancer. 2023;128(8):1415–1417. doi: 10.1038/s41416-023-02181-6.
  • Baxi V, Lee G, Duan C, Pandya D, Cohen DN, Edwards R, Chang H, Li J, Elliott H, Pokkalla H. et al. Association of artificial intelligence-powered and manual quantification of programmed death-ligand 1 (PD-L1) expression with outcomes in patients treated with nivolumab ± ipilimumab. Mod Pathol. 2022;35(11):1529–1539. doi: 10.1038/s41379-022-01119-2.
  • Myers JA, Miller JS. Exploring the NK cell platform for cancer immunotherapy. Nat Rev Clin Oncol. 2021;18(2):85–100. doi: 10.1038/s41571-020-0426-7.
  • Fenis A, Demaria O, Gauthier L, Vivier E, Narni-Mancinelli E. New immune cell engagers for cancer immunotherapy. Nat Rev Immunol. 2024;24(7):471–486. doi: 10.1038/s41577-023-00982-7.
  • Vallera DA, Ferrone S, Kodal B, Hinderlie P, Bendzick L, Ettestad B, Hallstrom C, Zorko NA, Rao A, Fujioka N. et al. NK-Cell-Mediated Targeting of Various Solid Tumors Using a B7-H3 Tri-Specific Killer Engager in vitro and in vivo. Cancers (Basel). 2020;12(9):2659. doi: 10.3390/cancers12092659.
  • Colomar-Carando N, Gauthier L, Merli P, Loiacono F, Canevali P, Falco M, Galaverna F, Rossi B, Bosco F, Caratini M. et al. Exploiting natural killer cell engagers to control pediatric b-cell precursor acute lymphoblastic leukemia. Cancer Immunol Res. 2022;10(3):291–302. doi: 10.1158/2326-6066.CIR-21-0843.
  • Demaria O, Gauthier L, Vetizou M, Blanchard Alvarez A, Vagne C, Habif G, Batista L, Baron W, Belaïd N, Girard-Madoux M. et al. Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant. Cell Rep Med. 2022;3(10):100783. doi: 10.1016/j.xcrm.2022.100783.
  • Gauthier L, Virone-Oddos A, Beninga J, Rossi B, Nicolazzi C, Amara C, Blanchard-Alvarez A, Gourdin N, Courta J, Basset A. et al. Control of acute myeloid leukemia by a trifunctional NKp46-CD16a-NK cell engager targeting CD123. Nat Biotechnol. 2023;41(9):1296–1306. doi: 10.1038/s41587-022-01626-2.

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