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Original research

Modulation of blood T cell polyfunctionality and HVEM/BTLA expression are critical determinants of clinical outcome in anti-PD1-treated metastatic melanoma patients

, , , , , , , , , , , , , , & ORCID Icon show all
Article: 2372118 | Received 12 Feb 2024, Accepted 20 Jun 2024, Published online: 26 Jun 2024

References

  • Brahmer JR, Tykodi SS, Chow LQM, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al. Safety and activity of Anti–PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–14. doi:10.1056/NEJMoa1200694.
  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of Anti–PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–2454. doi:10.1056/NEJMoa1200690.
  • Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–1355. doi:10.1126/science.aar4060.
  • Bocquet-Tremoureux S, Scharbarg E, Nguyen JM, Varey E, Quereux G, Saint-Jean M, Peuvrel L, Khammari A, Dreno B. Efficacy and safety of nivolumab in metastatic melanoma: real-world practice. Eur J Dermatol. 2019 juin 1;29(3):315–321. doi:10.1684/ejd.2019.3558.
  • Conroy M, Naidoo J. Immune-related adverse events and the balancing act of immunotherapy. Nat Commun. 2022;13(1):392. doi:10.1038/s41467-022-27960-2.
  • Vilain RE, Menzies AM, Wilmott JS, Kakavand H, Madore J, Guminski A, Liniker E, Kong BY, Cooper AJ, Howle JR, et al. Dynamic changes in PD-L1 expression and immune infiltrates early during treatment predict response to PD-1 blockade in Melanoma. Clin Cancer Res. 2017;23(17):5024–5033. doi:10.1158/1078-0432.CCR-16-0698.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23–34. doi:10.1056/NEJMoa1504030.
  • Hugo W, Shi H, Sun L, Piva M, Song C, Kong X, Moriceau G, Hong A, Dahlman K, Johnson D, et al. Non-genomic and immune evolution of Melanoma Acquiring MAPKi resistance. Cell. 2015;162(6):1271–1285. doi:10.1016/j.cell.2015.07.061.
  • Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, Albright A, Cheng JD, Kang SP, Shankaran V, et al. IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127(8):2930–2940. doi:10.1172/JCI91190.
  • Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–571. doi:10.1038/nature13954.
  • Cabrita R, Lauss M, Sanna A, Donia M, Skaarup Larsen M, Mitra S, Johansson I, Phung B, Harbst K, Vallon-Christersson J, et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature. 2020;577(7791):561–565. doi:10.1038/s41586-019-1914-8.
  • Helmink BA, Reddy SM, Gao J, Zhang S, Basar R, Thakur R, Yizhak K, Sade-Feldman M, Blando J, Han G, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020;577(7791):549–555. doi:10.1038/s41586-019-1922-8.
  • Tiako Meyo M, Jouinot A, Giroux-Leprieur E, Fabre E, Wislez M, Alifano M, Leroy K, Boudou-Rouquette P, Tlemsani C, Khoudour N, et al. Predictive value of soluble PD-1, PD-L1, VEGFA, CD40 Ligand and CD44 for Nivolumab therapy in advanced non-small cell lung cancer: a case-control study. Cancers (Basel). 2020;12(2):473. doi:10.3390/cancers12020473.
  • Okuma Y, Hosomi Y, Nakahara Y, Watanabe K, Sagawa Y, Homma S. High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer. Lung Cancer. 2017;104:1–6. doi:10.1016/j.lungcan.2016.11.023.
  • Mazzaschi G, Minari R, Zecca A, Cavazzoni A, Ferri V, Mori C, Squadrilli A, Bordi P, Buti S, Bersanelli M, et al. Soluble PD-L1 and circulating CD8+PD-1+ and NK cells enclose a prognostic and predictive immune effector score in immunotherapy treated NSCLC patients. Lung Cancer. 2020;148:1–11. doi:10.1016/j.lungcan.2020.07.028.
  • Machiraju D, Wiecken M, Lang N, Hülsmeyer I, Roth J, Schank TE, Eurich R, Halama N, Enk A, Hassel JC, et al. Soluble immune checkpoints and T-cell subsets in blood as biomarkers for resistance to immunotherapy in melanoma patients. Oncoimmunology. 2021;10(1):1926762. doi:10.1080/2162402X.2021.1926762.
  • Mitsuhashi A, Okuma Y. Perspective on immune oncology with liquid biopsy, peripheral blood mononuclear cells, and microbiome with non-invasive biomarkers in cancer patients. Clin Transl Oncol. 2018;20(8):966–974. doi:10.1007/s12094-017-1827-7.
  • An HJ, Chon HJ, Kim C. Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors. Int J Mol Sci. 2021;22(17):9414. doi:10.3390/ijms22179414.
  • Verronèse E, Delgado A, Vg J, Garin G, Guillemaut S, Tredan O, Ray-Coquard I, Bachelot T, N’Kodia A, Bardin-Dit-Courageot C, et al. Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay. Oncoimmunology. 2016;5(3):e1100791. doi:10.1080/2162402X.2015.1100791.
  • Granier C, De Guillebon E, Blanc C, Roussel H, Badoual C, Colin E, Saldmann A, Gey A, Oudard S, Tartour E, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open. 2017;2(2):e000213. doi:10.1136/esmoopen-2017-000213.
  • Duchemann B, Naigeon M, Auclin E, Ferrara R, Cassard L, Jouniaux JM, Boselli L, Grivel J, Desnoyer A, Danlos F-X, et al. CD8+PD-1+ to CD4+PD-1+ ratio (PERLS) is associated with prognosis of patients with advanced NSCLC treated with PD-(L)1 blockers. J Immunother Cancer. 2022;10(2):e004012. doi:10.1136/jitc-2021-004012.
  • Capone M, Giannarelli D, Mallardo D, Madonna G, Festino L, Grimaldi AM, Vanella V, Simeone E, Paone M, Palmieri G, et al. Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab. J Immunother Cancer. 2018;6(1):74. doi:10.1186/s40425-018-0383-1.
  • Garcia-Marquez MA, Thelen M, Reinke S, Keller D, Wennhold K, Lehmann J, Veldman J, Borchmann S, Rosenwald A, Sasse S, et al. Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma. Leukemia. 2022;36(3):760–771. doi:10.1038/s41375-021-01421-z.
  • Pirozyan MR, McGuire HM, Emran AA, Tseng HY, Tiffen JC, Lee JH, Carlino MS, Menzies AM, Long GV, Scolyer RA, et al. Pretreatment innate cell populations and CD4 T Cells in Blood Are Associated with Response to Immune Checkpoint Blockade in Melanoma Patients. Front Immunol. 2020;11:372. doi:10.3389/fimmu.2020.00372.
  • Osa A, Uenami T, Koyama S, Fujimoto K, Okuzaki D, Takimoto T, Hirata H, Yano Y, Yokota S, Kinehara Y, et al. Clinical implications of monitoring nivolumab immunokinetics in non–small cell lung cancer patients. JCI Insight. 2018;3(19):e59125, 59125. doi:10.1172/jci.insight.59125.
  • Sedy JR, Gavrieli M, Potter KG, Hurchla MA, Lindsley RC, Hildner K, Scheu S, Pfeffer K, Ware CF, Murphy TL, et al. B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol. 2005;6(1):90–98. doi:10.1038/ni1144.
  • Lee YS, O’Brien LJ, Walpole CM, Pearson FE, Leal-Rojas IM, Masterman KA, Atkinson V, Barbour A, Radford KJ. Human CD141+ dendritic cells (cDC1) are impaired in patients with advanced melanoma but can be targeted to enhance anti-PD-1 in a humanized mouse model. J Immunother Cancer. 2021;9(3):e001963. doi:10.1136/jitc-2020-001963.
  • Jongbloed SL, Kassianos AJ, McDonald KJ, Clark GJ, Ju X, Angel CE, Chen CJJ, Dunbar PR, Wadley RB, Jeet V, et al. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med. 2010;207(6):1247–1260. doi:10.1084/jem.20092140.
  • Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, et al. Batf3 deficiency reveals a critical role for CD8α+Dendritic cells in cytotoxic T cell immunity. Science. 2008;322(5904):1097–1100. doi:10.1126/science.1164206.
  • Sánchez-Paulete AR, Cueto FJ, Martínez-López M, Labiano S, Morales-Kastresana A, Rodríguez-Ruiz ME, Jure-Kunkel M, Azpilikueta A, Aznar MA, Quetglas JI, et al. Cancer immunotherapy with immunomodulatory Anti-CD137 and Anti–PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov. 2016;6(1):71–79. doi:10.1158/2159-8290.CD-15-0510.
  • Teijeira A, Garasa S, Luri-Rey C, de Andrea C, Gato M, Molina C, Kaisho T, Cirella A, Azpilikueta A, Wculek SK, et al. Depletion of conventional type-1 dendritic cells in established tumors suppresses immunotherapy efficacy. Cancer Res. 2022 déc 2;82(23):4373–4385. doi:10.1158/0008-5472.CAN-22-1046.
  • Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R, Jordan S, Casanova-Acebes M, Khudoynazarova M, Agudo J, Tung N, et al. Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF Inhibition. Immunity. 2016;44(4):924–938. doi:10.1016/j.immuni.2016.03.012.
  • Voissière A, Gomez-Roca C, Chabaud S, Rodriguez C, Nkodia A, Berthet J, Montane L, Bidaux A-S, Treilleux I, Eberst L, et al. The CSF-1R inhibitor pexidartinib affects FLT3-dependent DC differentiation and may antagonize durvalumab effect in patients with advanced cancers. Sci Transl Med. 2024;16(731):eadd1834. doi:10.1126/scitranslmed.add1834.
  • Mamessier E, Sylvain A, Thibult ML, 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.
  • Perrot I, Deauvieau F, Massacrier C, Hughes N, Garrone P, Durand I, Demaria O, Viaud N, Gauthier L, Blery M, et al. TLR3 and rig-like receptor on myeloid dendritic cells and rig-like receptor on human NK cells are both mandatory for production of IFN-γ in response to double-stranded RNA. J Immunol. 2010;185(4):2080–2088. doi:10.4049/jimmunol.1000532.
  • Gorski KS, Waller EL, Bjornton-Severson J, Hanten JA, Riter CL, Kieper WC, Gorden KB, Miller JS, Vasilakos JP, Tomai MA, et al. Distinct indirect pathways govern human NK-cell activation by TLR-7 and TLR-8 agonists. Int Immunol. 2006;18(7):1115–1126. doi:10.1093/intimm/dxl046.
  • Deauvieau F, Ollion V, Doffin AC, Achard C, Fonteneau JF, Verronese E, Durand I, Ghittoni R, Marvel J, Dezutter‐Dambuyant C, et al. Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells. Int J Cancer. 2015;136(5):1085–1094. doi:10.1002/ijc.29087.
  • Manjarrez-Orduño N, Menard LC, Kansal S, Fischer P, Kakrecha B, Jiang C, Cunningham M, Greenawalt D, Patel V, Yang M, et al. Circulating T cell subpopulations correlate with immune responses at the tumor site and clinical response to PD1 inhibition in non-small cell lung cancer. Front Immunol. 2018;9:1613. doi:10.3389/fimmu.2018.01613.
  • Demerlé C, Gorvel L, Olive D. BTLA-HVEM couple in health and diseases: insights for immunotherapy in lung cancer. Front Oncol. 2021;11:682007. doi:10.3389/fonc.2021.682007.
  • Cai G, Anumanthan A, Brown JA, Greenfield EA, Zhu B, Freeman GJ. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat Immunol. 2008;9(2):176–185. doi:10.1038/ni1554.
  • Tamada K, Shimozaki K, Chapoval AI, Zhai Y, Su J, Chen SF, Hsieh S-L, Nagata S, Ni J, Chen L, et al. LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response. J Immunol. 2000;164(8):4105–4110. doi:10.4049/jimmunol.164.8.4105.
  • Demerlé C, Gorvel L, Mello M, Pastor S, Degos C, Zarubica A, Angelis F, Fiore F, Nunes JA, Malissen B, et al. Anti-HVEM mAb therapy improves antitumoral immunity both in vitro and in vivo, in a novel transgenic mouse model expressing human HVEM and BTLA molecules challenged with HVEM expressing tumors. J Immunother Cancer. 2023;11(5):e006348. doi:10.1136/jitc-2022-006348.
  • Liu J, Li J, He M, Zhang GL, Zhao Q. Distinct changes of BTLA and HVEM expressions in circulating CD4+ and CD8+ T cells in hepatocellular carcinoma patients. J Immunol Res. 2018;2018:1–8. doi:10.1155/2018/4561571.
  • Carter LL, Carreno BM. Cytotoxic T-lymphocyte antigen-4 and programmed death-1 function as negative regulators of lymphocyte activation. Immunol Res. 2003;28(1):49–60. doi:10.1385/IR:28:1:49.
  • Chemnitz JM, Lanfranco AR, Braunstein I, Riley JL. B and T lymphocyte attenuator-mediated signal transduction provides a potent inhibitory signal to primary human CD4 T cells that can be initiated by multiple phosphotyrosine motifs. J Immunol. 2006;176(11):6603–6614. doi:10.4049/jimmunol.176.11.6603.
  • Pasero C, Truneh A, Olive D. Cosignaling molecules around LIGHT-HVEM-BTLA: from immune activation to therapeutic targeting. Curr Mole Medi. 2009;9(7):911–927. doi:10.2174/156652409789105589.
  • Walsh DA, Borges da Silva H, Beura LK, Peng C, Hamilton SE, Masopust D, Jameson SC. The Functional Requirement for CD69 in Establishment of Resident Memory CD8+ T Cells Varies with Tissue Location. J Immunol. 2019;203(4):946–955. doi:10.4049/jimmunol.1900052.
  • Lao J, Xu H, Liang Z, Luo C, Shu L, Xie Y, Wu Y, Hao Y, Yuan Y. Peripheral changes in T cells predict efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer. Immunobiology. 2023;228(3):152391. doi:10.1016/j.imbio.2023.152391.
  • Kim KH, Hur JY, Cho J, Ku BM, Koh J, Koh JY, Sun J-M, Lee S-H, Ahn JS, Park K, et al. Immune-related adverse events are clustered into distinct subtypes by T-cell profiling before and early after anti-PD-1 treatment. Oncoimmunology. 2020;9(1):1722023. doi:10.1080/2162402X.2020.1722023.
  • Moskophidis D, Lechner F, Pircher H, Zinkernagel RM. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature. 1993;362(6422):758–761. doi:10.1038/362758a0.
  • Rubatto M, Fava P, Stanganelli I, Ribero S, Pigozzo J, Di Giacomo AM, Ridolfi L, Tronconi MC, Trojaniello C, Bersanelli M, et al. Discontinuation of anti-PD1 in advanced melanoma: an observational retrospective study from the Italian Melanoma Intergroup. Eur J Cancer. 2023;187:25–35. doi:10.1016/j.ejca.2023.03.020.
  • Sordo-Bahamonde C, Lorenzo-Herrero S, Granda-Díaz R, Martínez-Pérez A, Aguilar-García C, Rodrigo JP, García-Pedrero JM, Gonzalez S. Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy. Mol Cancer. 2023;22(1):142. doi:10.1186/s12943-023-01845-4.