4,336
Views
33
CrossRef citations to date
0
Altmetric
Original Research

TIGIT+ TIM-3+ NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus‑related hepatocellular carcinoma

, MDORCID Icon, , MD, , MD, , MD, , MD, , MD, PhD, , MD, PhD & , MD, PhD show all
Article: 1942673 | Received 18 Feb 2021, Accepted 09 Jun 2021, Published online: 28 Jun 2021

References

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–13. doi:10.3322/caac.21660.
  • Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014;60(6):2099–2108. doi:10.1002/hep.27406.
  • El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264–1273.e1. doi:10.1053/j.gastro.2011.12.061.
  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–132. doi:10.3322/caac.21338.
  • Bald T, Krummel MF, Smyth MJ, Barry KC. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies. Nat Immunol. 2020;21(8):835–847. doi:10.1038/s41590-020-0728-z.
  • Chen Y, Tian Z. Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer. Cell Mol Immunol. 2021;18(1):57–72. doi:10.1038/s41423-020-00561-z.
  • Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, André P, Dieu-Nosjean MC, Alifano M, Régnard JF, et al. 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.
  • 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.
  • Jie HB, Schuler PJ, Lee SC, Srivastava RM, Argiris A, Ferrone S, Whiteside TL, Ferris RLCTLA. 4⁺ Regulatory T Cells Increased in Cetuximab-Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor Prognosis. Cancer Res. 2015;75(11):2200–2210. doi:10.1158/0008-5472..
  • Zhang QF, Yin WW, Xia Y, Yi YY, He QF, Wang X, Ren H, Zhang DZ. Liver-infiltrating CD11b-CD27- NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression. Cell Mol Immunol. 2017;14(10):819–829. doi:10.1038/cmi.2016.28.
  • Malmberg KJ, Carlsten M, Björklund A, Sohlberg E, Bryceson YT, Ljunggren HG. Natural killer cell-mediated immunosurveillance of human cancer. Semin Immunol. 2017;31:20–29. doi:10.1016/j.smim.2017.08.002.
  • Muntasell A, Ochoa MC, Cordeiro L, Berraondo P. López-Díaz de Cerio A, Cabo M, López-Botet M, Melero I. Targeting NK-cell checkpoints for cancer immunotherapy. Curr Opin Immunol. 2017;45:73–81. doi:10.1016/j.coi.2017.01.003.
  • 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.
  • Sun C, Xu J, Huang Q, Huang M, Wen H, Zhang C, Wang J, Song J, Zheng M, Sun H, et al. High NKG2A expression contributes to NK cell exhaustion and predicts a poor prognosis of patients with liver cancer. Oncoimmunology. 2016;6(1):e1264562. doi:10.1080/2162402X.2016.1264562.
  • Seo H, Jeon I, Kim BS, Park M, Bae EA, Song B, Koh CH, Shin KS, Kim IK, Choi K, et al. IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours. Nat Commun. 2017;8(1):15776. doi:10.1038/ncomms15776.
  • Cai L, Zhang Z, Zhou L, Wang H, Fu J, Zhang S, Shi M, Zhang H, Yang Y, Wu H, et al. Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients. Clin Immunol. 2008;129(3):428–437. doi:10.1016/j.clim.2008.08.012.
  • Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, Tom I, Ivelja S, Refino CJ, Clark H, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48–57. doi:10.1038/ni.1674.
  • Dao TN, Utturkar S, Atallah Lanman N, Matosevic STIM-3. Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation. Cancers (Basel). 2020;12(9):2417. doi:10.3390/cancers12092417.
  • So EC, Khaladj-Ghom A, Ji Y, Amin J, Song Y, Burch E, Zhou H, Sun H, Chen S, Bentzen S, et al. NK cell expression of Tim-3: first impressions matter. Immunobiology. 2019;224(3):362–370. doi:10.1016/j.imbio.2019.03.001.
  • Ju Y, Hou N, Meng J, Wang X, Zhang X, Zhao D, Liu Y, Zhu F, Zhang L, Sun W, et al. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B. J Hepatol. 2010;52(3):322–329. doi:10.1016/j.jhep.2009.12.005.
  • Department of Medical Administration, National Health and Health Commission of the People’s Republic of China. [Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)]. Zhonghua Gan Zang Bing Za Zhi. 2020;28( 2):112–128. Chinese. doi: 10.3760/cma.j..1007-3418.2020.02.004.
  • Chinese Society of Hepatology,Chinese Medical Association. [Chinese guidelines on the management of liver cirrhosis]. Zhonghua Gan Zang Bing Za Zhi. 2019;27( 11):846–865. Chinese. doi: 10.3760/cma.j..1007-3418.2019.11.008.
  • Song Y, Wang B, Song R, Hao Y, Wang D, Li Y, Jiang Y, Xu L, Ma Y, Zheng H, et al. T-cell Immunoglobulin and ITIM Domain Contributes to CD8+ T-cell Immunosenescence. Aging Cell. 2018;17(2):e12716. doi:10.1111/acel.12716.
  • Bi J, Tian Z. NK Cell Exhaustion. Front Immunol. 2017;8:760. doi:10.3389/fimmu.2017.00760.
  • Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948):1109–1117. doi:10.1016/S0140-6736(14)60958-2.
  • JS W, SP D, Minor D, FS H, Gutzmer R, Neyns B, Hoeller C, NI K, Jr MWH, CD L, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16(4):375–384. doi:10.1016/S1470-2045(15)70076-8.
  • Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486–499. doi:10.1038/nri3862.
  • Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity. 2016;44(5):989–1004. doi:10.1016/j.immuni.2016.05.001.
  • Wu L, Mao L, Liu JF, Chen L, Yu GT, Yang LL, Wu H, Bu LL, Kulkarni AB, Zhang WF, et al. Blockade of TIGIT/CD155 Signaling Reverses T-cell Exhaustion and Enhances Antitumor Capability in Head and Neck Squamous Cell Carcinoma. Cancer Immunol Res. 2019;7(10):1700–1713. doi:10.1158/2326-6066.CIR-18-0725.
  • Ostroumov D, Duong S, Wingerath J, Woller N, Manns MP, Timrott K, Kleine M, Ramackers W, Roessler S, Nahnsen S, et al. Transcriptome Profiling Identifies TIGIT as a Marker of T-Cell Exhaustion in Liver Cancer. Hepatology. 2021;73(4):1399–1418. doi:10.1002/hep.31466.
  • Avery L, Filderman J, Szymczak-Workman AL, Kane LP. Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion. Proc Natl Acad Sci U S A. 2018;115(10):2455–2460. doi:10.1073/pnas.1712107115.
  • Zhang Y, Cai P, Li L, Shi L, Chang P, Liang T, Yang Q, Liu Y, Wang L, Hu L. Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients. Int Immunopharmacol. 2017;43:210–218. doi:10.1016/j.intimp.2016.12.024.
  • Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2):e000957. doi:10.1136/jitc-2020-000957.
  • Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, Tom I, Ivelja S, Refino CJ, Clark H, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48–57. doi:10.1038/ni.1674.
  • Wang F, Hou H, Wu S, Tang Q, Liu W, Huang M, Yin B, Huang J, Mao L, Lu Y, et al. TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals. Eur J Immunol. 2015;45(10):2886–2897. doi:10.1002/eji.201545480.
  • Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245–1252. doi:10.1038/ni1271.
  • Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T, et al. Corrigendum: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 2016;536(7616):359. doi:10.1038/nature17421.
  • 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.
  • Xu L, Huang Y, Tan L, Yu W, Chen D, Lu C, He J, Wu G, Liu X, Zhang Y. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma. Int Immunopharmacol. 2015;29(2):635–641. doi:10.1016/j.intimp.2015.09.017.
  • Shehata HM, Hoebe K, Chougnet CA. The aged nonhematopoietic environment impairs natural killer cell maturation and function. Aging Cell. 2015;14(2):191–199. doi:10.1111/acel.12303.
  • Simonetta F, Pradier A, Bosshard C, Masouridi-Levrat S, Chalandon Y, Roosnek E. NK Cell Functional Impairment after Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Reduced Levels of T-bet and Eomesodermin. J Immunol. 2015;195(10):4712–4720. doi:10.4049/jimmunol.1501522.
  • 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.
  • Dielmann A, Letsch A, Nonnenmacher A, Miller K, Keilholz U, Busse A. Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients. Cancer Immunol Immunother. 2016;65(2):181–192. doi:10.1007/s00262-015-1786-1.
  • Björkström NK, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson MA, Björklund AT, Flodström-Tullberg M, Michaëlsson J, Rottenberg ME, et al. Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood. 2010;116(19):3853–3864. doi:10.1182/blood-2010-04-281675.
  • Collins A, Rothman N, Liu K, Reiner SL. Eomesodermin and T-bet mark developmentally distinct human natural killer cells. JCI Insight. 2017;2(5):e90063. doi:10.1172/jci.insight.90063.
  • 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.
  • Tan S, Xu Y, Wang Z, Wang T, Du X, Song X, Guo X, Peng J, Zhang J, Liang Y, et al. Tim-3 Hampers Tumor Surveillance of Liver-Resident and Conventional NK Cells by Disrupting PI3K Signaling. Cancer Res. 2020;80(5):1130–1142. doi:10.1158/0008-5472.CAN-19-2332.
  • Liu X, Li M, Wang X, Dang Z, Jiang Y, Wang X, Kong Y, Yang Z. PD-1+ TIGIT+ CD8+ T cells are associated with pathogenesis and progression of patients with hepatitis B virus-related hepatocellular carcinoma. Cancer Immunol Immunother. 2019;68(12):2041–2054. doi:10.1007/s00262-019-02426-5.