NKG2D及其配体治疗胃癌的研究进展

doi:10.3760/cma.j.issn.1007-1245.2023.20.007

摘要/Abstract

摘要：

自然杀伤细胞2D（natural killer cell 2D，NKG2D）及其配体在NK细胞识别、启动、增强或抑制淋巴细胞效应功能上发挥着重要作用。近年来，随着肿瘤免疫逃避研究的深入，NK细胞上的NKG2D受体成为一个研究热门。胃癌作为严重影响人类寿命的疾病，其治疗一直是难以突破的难题。近年来，针对癌症的免疫治疗取得了重大突破。NKG2D及其配体可能是一个潜在的免疫治疗方向，故本文综述了NKG2D及其配体治疗胃癌的研究进展。

关键词:

胃癌, NK细胞, 肿瘤免疫, 免疫逃避, NKG2D, 进展

Abstract:

Natural killer cell 2D (NKG2D) and its ligands play an important role in the recognition, initiation, enhancement, or inhibition of lymphocyte effects in NK cells. In recent years, the NKG2D receptor on NK cells has become a hot research topic with the deepening of tumor immune evasion research. As a serious disease affecting human life span, gastric cancer's treatment has been a difficult problem. In recent years, major breakthroughs have been made in the immunotherapy of cancer. NKG2D and its ligands may be a potential direction of immunotherapy. Therefore, this paper reviews the research progress of NKG2D and its ligands in the treatment of gastric cancer.

Key words:

Gastric cancer, NK cells, Tumor immunity, Immune evasion, NKG2D, Progress

李宗睿刘为朋胡宝光.

NKG2D及其配体治疗胃癌的研究进展 [J]. 国际医药卫生导报, 2023, 29(20): 2852-2856.

Li Zongrui, Liu Weipeng, Hu Baoguang.

Research progress of NKG2D and its ligands in treatment of gastric cancer [J]. International Medicine and Health Guidance News, 2023, 29(20): 2852-2856.

参考文献

[1] Lanier LL. NKG2D receptor and its ligands in host defense [J]. Cancer Immunol Res, 2015, 3(6): 575-582. DOI: 10.1158/2326-6066.CIR-15-0098.
[2] Cerboni C, Mousavi-Jazi M, Linde A, et al. Human cytomegalovirus strain-dependent changes in NK cell recognition of infected fibroblasts [J]. J Immunol, 2000, 164(9): 4775-4782. DOI: 10.4049/jimmunol.164.9.4775.
[3] Bauer S, Groh V, Wu J, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA [J]. Science, 1999, 285(5428): 727-729. DOI: 10.1126/science.285.5428.727.
[4] Garrity D, Call ME, Feng J, et al. The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure [J]. Proc Natl Acad Sci U S A, 2005, 102(21): 7641-7646. DOI: 10.1073/pnas.0502439102.
[5] Diefenbach A, Tomasello E, Lucas M, et al. Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D [J]. Nat Immunol, 2002, 3(12): 1142-1149. DOI: 10.1038/ni858.
[6] McFarland BJ, Kortemme T, Yu SF, et al. Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands [J]. Structure, 2003, 11(4): 411-422. DOI: 10.1016/s0969-2126(03)00047-9.
[7] Di Santo JP. Natural killer cell developmental pathways: a question of balance [J]. Annu Rev Immunol, 2006, 24: 257-286. DOI: 10.1146/annurev.immunol.24. 021605.090700.
[8] Raulet DH, Gasser S, Gowen BG, et al. Regulation of ligands for the NKG2D activating receptor [J]. Annu Rev Immunol, 2013, 31: 413-441. DOI: 10.1146/annurev-immunol-032712-095951.
[9] Raulet DH. Roles of the NKG2D immunoreceptor and its ligands [J]. Nat Rev Immunol, 2003, 3(10): 781-790. DOI: 10.1038/nri1199.
[10] Champsaur M, Lanier LL. Effect of NKG2D ligand expression on host immune responses [J]. Immunol Rev, 2010, 235(1): 267-285. DOI: 10.1111/j.0105-2896.2010.00893.x.
[11] Le Bert N, Gasser S. Advances in NKG2D ligand recognition and responses by NK cells [J]. Immunol Cell Biol, 2014, 92(3): 230-236. DOI: 10.1038/icb.2013.111.
[12] Eagle RA, Trowsdale J. Promiscuity and the single receptor: NKG2D [J]. Nat Rev Immunol, 2007, 7(9): 737-744. DOI: 10.1038/nri2144.
[13] Curio S, Lin W, Bromley C, et al. NKG2D fine-tunes the local inflammatory response in colorectal cancer [J]. Cancers (Basel), 2023, 15(6): 1792. DOI: 10.3390/cancers15061792.
[14] Dutta S, Ganguly A, Chatterjee K, et al. Targets of immune escape mechanisms in cancer: basis for development and evolution of cancer immune checkpoint inhibitors [J]. Biology (Basel), 2023, 12(2): 218. DOI: 10.3390/biology12020218.
[15] Baragaño Raneros A, Suarez-Álvarez B, López-Larrea C. Secretory pathways generating immunosuppressive NKG2D ligands: new targets for therapeutic intervention [J]. Oncoimmunology, 2014, 3: e28497. DOI: 10.4161/onci.28497.
[16] Eagle RA, Jafferji I, Barrow AD. Beyond stressed self: evidence for NKG2D ligand expression on healthy cells [J]. Curr Immunol Rev, 2009, 5(1): 22-34. DOI: 10.2174/157339509787314369.
[17] Yu L, Sun L, Liu X, et al. The imbalance between NKG2A and NKG2D expression is involved in NK cell immunosuppression and tumor progression of patients with hepatitis B virus-related hepatocellular carcinoma [J]. Hepatol Res, 2023, 53(5): 417-431. DOI: 10.1111/hepr.13877.
[18] Wensveen FM, Jelenčić V, Polić B. NKG2D: a master regulator of immune cell responsiveness [J]. Front Immunol, 2018, 9: 441. DOI: 10.3389/fimmu.2018.00441.
[19] Groh V, Wu J, Yee C, et al. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation [J]. Nature, 2002, 419(6908): 734-738. DOI: 10.1038/nature01112.
[20] Curio S, Jonsson G, Marinović S. A summary of current NKG2D-based CAR clinical trials [J]. Immunother Adv, 2021, 1(1): ltab018. DOI: 10.1093/immadv/ltab018.
[21] Molfetta R, Quatrini L, Capuano C, et al. c-Cbl regulates MICA- but not ULBP2-induced NKG2D down-modulation in human NK cells [J]. Eur J Immunol, 2014, 44(9): 2761-2770. DOI: 10.1002/eji.201444512.
[22] Quatrini L, Molfetta R, Zitti B, et al. Ubiquitin-dependent endocytosis of NKG2D-DAP10 receptor complexes activates signaling and functions in human NK cells [J]. Sci Signal, 2015, 8(400): ra108. DOI: 10.1126/scisignal.aab2724.
[23] Roda-Navarro P, Reyburn HT. The traffic of the NKG2D/Dap10 receptor complex during natural killer (NK) cell activation [J]. J Biol Chem, 2009, 284(24): 16463-16472. DOI: 10.1074/jbc.M808561200.
[24] Doubrovina ES, Doubrovin MM, Vider E, et al. Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma [J]. J Immunol, 2003, 171(12): 6891-6899. DOI: 10.4049/jimmunol.171.12.6891.
[25] Chitadze G, Bhat J, Lettau M, et al. Generation of soluble NKG2D ligands: proteolytic cleavage, exosome secretion and functional implications [J]. Scand J Immunol, 2013, 78(2): 120-129. DOI: 10.1111/sji.12072.
[26] Chitadze G, Lettau M, Bhat J, et al. Shedding of endogenous MHC class I-related chain molecules A and B from different human tumor entities: heterogeneous involvement of the "a disintegrin and metalloproteases" 10 and 17 [J]. Int J Cancer, 2013, 133(7): 1557-1566. DOI: 10.1002/ijc.28174.
[27] Zingoni A, Cecere F, Vulpis E, et al. Genotoxic stress induces senescence-associated ADAM10-dependent release of NKG2D MIC ligands in multiple myeloma cells [J]. J Immunol, 2015, 195(2): 736-748. DOI: 10.4049/jimmunol.1402643.
[28] Ashiru O, Boutet P, Fernández-Messina L, et al. Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes [J]. Cancer Res, 2010, 70(2): 481-489. DOI: 10.1158/0008-5472.CAN-09-1688.
[29] Kumar V, Yi Lo PH, Sawai H, et al. Soluble MICA and a MICA variation as possible prognostic biomarkers for HBV-induced hepatocellular carcinoma [J]. PLoS One, 2012, 7(9):e44743. DOI: 10.1371/journal.pone.0044743.
[30] Tamaki S, Kawakami M, Ishitani A, et al. Soluble MICB serum levels correlate with disease stage and survival rate in patients with oral squamous cell carcinoma [J]. Anticancer Res, 2010, 30(10): 4097-4101.
[31] Zhao YK, Jia CM, Yuan GJ, et al. Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors [J]. Genet Mol Res, 2015, 14(2): 7233-7240. DOI: 10.4238/2015.June.29.16.
[32] Holdenrieder S, Stieber P, Peterfi A, et al. Soluble MICA in malignant diseases [J]. Int J Cancer, 2006, 118(3): 684-687. DOI: 10.1002/ijc.21382.
[33] Maccalli C, Giannarelli D, Chiarucci C, et al. Soluble NKG2D ligands are biomarkers associated with the clinical outcome to immune checkpoint blockade therapy of metastatic melanoma patients [J]. Oncoimmunology, 2017, 6(7): e1323618. DOI: 10.1080/2162402X. 2017.1323618.
[34] Barber A, Zhang T, Megli CJ, et al. Chimeric NKG2D receptor-expressing T cells as an immunotherapy for multiple myeloma [J]. Exp Hematol, 2008, 36(10): 1318-1328. DOI: 10.1016/j.exphem.2008.04.010.
[35] Barber A, Zhang T, DeMars LR, et al. Chimeric NKG2D receptor-bearing T cells as immunotherapy for ovarian cancer [J]. Cancer Res, 2007, 67(10): 5003-5008. DOI: 10.1158/0008-5472.CAN-06-4047.
[36] Fernández L, Metais JY, Escudero A, et al. Memory T cells expressing an NKG2D-CAR efficiently target osteosarcoma cells [J]. Clin Cancer Res, 2017, 23(19): 5824-5835. DOI: 10.1158/1078-0432.CCR-17-0075.
[37] Chang YH, Connolly J, Shimasaki N, et al. A chimeric receptor with NKG2D specificity enhances natural killer cell activation and killing of tumor cells [J]. Cancer Res, 2013, 73(6): 1777-1786. DOI: 10.1158/0008-5472.CAN-12-3558.
[38] Basher F, Jeng EK, Wong H, et al. Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC [J]. Oncotarget, 2016, 7(1): 814-830. DOI: 10.18632/oncotarget.6416.
[39] Han Y, Xie W, Song DG, et al. Control of triple-negative breast cancer using ex vivo self-enriched, costimulated NKG2D CAR T cells [J]. J Hematol Oncol, 2018, 11(1): 92. DOI: 10.1186/s13045-018-0635-z.
[40] Fernández-Sánchez A, Baragaño Raneros A, Carvajal Palao R, et al. DNA demethylation and histone H3K9 acetylation determine the active transcription of the NKG2D gene in human CD8+ T and NK cells [J]. Epigenetics, 2013, 8(1): 66-78. DOI: 10.4161/epi.23115.
[41] Raneros AB, Minguela A, Rodriguez RM, et al. Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated immune recognition [J]. Oncotarget, 2017, 8(19):31959-31976. DOI: 10.18632/oncotarget.16657.
[42] Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer [J]. CA Cancer J Clin, 2021, 71(3): 264-279. DOI: 10.3322/caac.21657.
[43] Seeneevassen L, Bessède E, Mégraud F, et al. Gastric cancer: advances in carcinogenesis research and new therapeutic strategies [J]. Int J Mol Sci, 2021, 22(7): 3418. DOI: 10.3390/ijms22073418.
[44] Wang FH, Zhang XT, Li YF, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2021 [J]. Cancer Commun (Lond), 2021, 41(8): 747-795. DOI: 10.1002/cac2.12193.
[45] Li K, Zhang A, Li X, et al. Advances in clinical immunotherapy for gastric cancer [J]. Biochim Biophys Acta Rev Cancer, 2021, 1876(2): 188615. DOI: 10.1016/j.bbcan.2021.188615.
[46] Janjigian YY, Maron SB, Chatila WK, et al. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial [J]. Lancet Oncol, 2020, 21(6): 821-831. DOI: 10.1016/S1470-2045(20)30169-8.
[47] Jemal A, Bray F, Center MM, et al. Global cancer statistics [J]. CA Cancer J Clin, 2011, 61(2): 69-90. DOI: 10.3322/caac.20107.
[48] Mimura K, Kamiya T, Shiraishi K, et al. Therapeutic potential of highly cytotoxic natural killer cells for gastric cancer [J]. Int J Cancer, 2014, 135(6): 1390-1398. DOI: 10.1002/ijc.28780.
[49] Liu X, Sun M, Yu S, et al. Potential therapeutic strategy for gastric cancer peritoneal metastasis by NKG2D ligands-specific T cells [J]. Onco Targets Ther, 2015, 8: 3095-3104. DOI: 10.2147/OTT.S91122.
[50] Lin F, Dai C, Ge X, et al. Prognostic significance and functional implication of immune activating receptor NKG2D in gastric cancer [J]. Biochem Biophys Res Commun, 2017, 487(3): 619-624. DOI: 10.1016/j.bbrc.2017.04.104.
[51] Zhou Z, Li J, Hong J, et al. Interleukin-15 and chemokine ligand 19 enhance cytotoxic effects of chimeric antigen receptor T cells using zebrafish xenograft model of gastric cancer [J]. Front Immunol, 2022, 13: 1002361. DOI: 10.3389/fimmu.2022.1002361.
[52] Tao K, He M, Tao F, et al. Development of NKG2D-based chimeric antigen receptor-T cells for gastric cancer treatment [J]. Cancer Chemother Pharmacol, 2018, 82(5): 815-827. DOI: 10.1007/s00280-018-3670-0.
[53] Li M, Zhi L, Yin M, et al. A novel bispecific chimeric PD1-DAP10/NKG2D receptor augments NK92-cell therapy efficacy for human gastric cancer SGC-7901 cell [J]. Biochem Biophys Res Commun, 2020, 523(3):745-752. DOI: 10.1016/j.bbrc.2020.01.005.
[54] Han B, Mao FY, Zhao YL, et al. Altered NKp30, NKp46, NKG2D, and DNAM-1 expression on circulating nk cells is associated with tumor progression in human gastric cancer [J]. J Immunol Res, 2018: 6248590. DOI: 10.1155/2018/6248590.
[55] Béziat V, Liu LL, Malmberg JA, et al. NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs [J]. Blood, 2013, 121(14): 2678-2688. DOI: 10.1182/blood-2012-10-459545.
[56] Zhang T, Scott JM, Hwang I, et al. Cutting edge: antibody-dependent memory-like NK cells distinguished by FcRγ deficiency [J]. J Immunol, 2013, 190(4): 1402-1406. DOI: 10.4049/jimmunol.1203034.
[57] Tran HC, Wan Z, Sheard MA, et al. TGFβR1 blockade with galunisertib (LY2157299) enhances anti-neuroblastoma activity of the anti-GD2 antibody dinutuximab (ch14.18) with natural killer cells [J]. Clin Cancer Res, 2017, 23(3): 804-813. DOI: 10.1158/1078-0432.CCR-16-1743.
[58] Chen Y, Chen B, Yang T, et al. Human fused NKG2D-IL-15 protein controls xenografted human gastric cancer through the recruitment and activation of NK cells [J]. Cell Mol Immunol, 2017, 14(3): 293-307. DOI: 10.1038/cmi.2015.81.