-
摘要: 近年来免疫检查点阻断在癌症治疗中的应用引起广泛关注。靶向PD-1、PD-L1或CTLA-4的药物在临床试验中仅有部分患者受益。确定新的免疫检查点，探索其作用机制将进一步发展肿瘤免疫疗法。TIGIT、CD226、CD112R和CD96是免疫细胞表达的一组免疫球蛋白超家族受体，与肿瘤细胞表达的Nectin/Necl家族配体（CD155、CD112）相互结合，在肿瘤免疫反应中发挥巨大作用，是新一代的免疫检查点。本文将对CD155、CD112、TIGIT、CD226、CD112R及CD96的分子结构与在肿瘤免疫反应中的作用进行阐述，探讨在癌症免疫治疗中的潜在应用。Abstract: In recent years, the application of immune checkpoint blockade to cancer therapy has attracted widespread attention. Antibodies targeting the related receptors PD-1, PD-L1, or CTLA-4 have benefited some patients but not others in clinical trials. Identification of more immune checkpoints and exploration of their mechanisms of action will contribute to broadening the efficacy of tumor immunotherapy. Among a new generation of immune checkpoints, TIGIT, CD226, CD112R, and CD96 are a group of immunoglobulin superfamily receptors expressed by immune cells that interact with nectin and nectin-like (Nectin/Necl) molecules (CD155, CD112) expressed by tumor cells, and play a huge role in tumor immune response. In this review, the molecular structures of CD155, CD112, TIGIT, CD226, CD112R, and CD96 and their roles in tumor immune response are reviewed, and their potential application in cancer immunotherapy is discussed.
-
表 1 免疫球蛋白超家族受体与Nectin/Necl家族配体结合
分子 别名 主要信号序列 配体 TIGIT WUCAM ITT，ITIM CD155，CD112，CD113，PVRL4 CD112R PVRIG ITIM CD112 CD96 TACTILE ITIM，YXXM CD155，CD111 CD226 DNAM-1 ITT CD155，CD112 
下载: 导出CSV
-
[1] Qin S, Xu L, Yi M, et al. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4[J]. Mol Cancer, 2019, 18(1):155. doi: 10.1186/s12943-019-1091-2 [2] Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance[J]. Annu Rev Pathol, 2021, 16:223-249. doi: 10.1146/annurev-pathol-042020-042741 [3] Gao J, Zheng Q, Xin N, et al. CD155, an onco‐immunologic molecule in human tumors[J]. Cancer Sci, 2017, 108(10):1934-1938. doi: 10.1111/cas.13324 [4] Takai Y, Miyoshi J, Ikeda W, et al. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation[J]. Nat Rev Mol Cell Biol, 2008, 9(8):603-615. doi: 10.1038/nrm2457 [5] Zhuo B, Li Y, Gu F, et al. Overexpression of CD155 relates to metastasis and invasion in osteosarcoma[J]. Oncol Lett, 2018, 15(5):7312-7318. [6] Li X, Das I, Lepletier A, et al. CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms[J]. J Clin Invest, 2018, 128(6):2613-2625. doi: 10.1172/JCI98769 [7] Zheng Q, Wang B, Gao J, et al. CD155 knockdown promotes apoptosis via AKT/Bcl-2/Bax in colon cancer cells[J]. J Cell Mol Med, 2018, 22(1):131-140. doi: 10.1111/jcmm.13301 [8] Hirota T, Irie K, Okamoto R, et al. Transcriptional activation of the mouse Necl-5/Tage4/PVR/CD155 gene by fibroblast growth factor or oncogenic Ras through the Raf-MEK-ERK-AP-1 pathway[J]. Oncogene, 2005, 24(13):2229-2235. doi: 10.1038/sj.onc.1208409 [9] Kono T, Imai Y, Yasuda S, et al. The CD155/poliovirus receptor enhances the proliferation of ras-mutated cells[J]. Int J Cancer, 2008, 122(2): 317-324. [10] Lepletier A, Madore J, O'Donnell JS, et al. Tumor CD155 expression is associated with resistance to anti-PD1 immunotherapy in metastatic melanoma[J]. Clin Cancer Res, 2020:2019-3925. [11] He W, Zhang H, Han F, et al. CD155T/TIGIT signaling regulates CD8+T-cell metabolism and promotes tumor progression in human gastric cancer[J]. Cancer Res, 2017, 77(22):6375-6388. doi: 10.1158/0008-5472.CAN-17-0381 [12] Wu L, Mao L, Liu JF, et al. Blockade of TIGIT/CD155 signaling reverses T-cell exhaustion and enhances antitumor capability in head and neck squamous cell carcinoma[J]. Cancer Immunol Res, 2019, 7(10):1700-1713. doi: 10.1158/2326-6066.CIR-18-0725 [13] Zhang H, Liu Q, Lei Y, et al. Direct interaction between CD155 and CD96 promotes immunosuppression in lung adenocarcinoma[J]. Cell Mol Immunol, 2020, 18(6):1575-1577. [14] Du X, de Almeida P, Manieri N, et al. CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1[J]. Proc Natl Acad Sci U S A, 2018, 115(50):E11731-E11740. doi: 10.1073/pnas.1814052115 [15] Husain B, Ramani SR, Chiang E, et al. A platform for extracellular interactome discovery identifies novel functional binding partners for the immune receptors B7-H3/CD276 and PVR/CD155[J]. Mol Cell Proteomics, 2019, 18(11):2310-2323. doi: 10.1074/mcp.TIR119.001433 [16] Sanchez-Correa B, Valhondo I, Hassouneh F, et al. DNAM-1 and the TIGIT/PVRIG/TACTILE axis: novel immune checkpoints for natural killer cell-based cancer immunotherapy[J]. Cancers (Basel), 2019, 11(6):877. doi: 10.3390/cancers11060877 [17] Whelan S, Ophir E, Kotturi MF, et al. PVRIG and PVRL2 are induced in cancer and inhibit CD8+ T-cell function[J]. Cancer Immunol Res, 2019, 7(2):257-268. doi: 10.1158/2326-6066.CIR-18-0442 [18] Jin HS, Park Y. Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy[J]. BMB Rep, 2021, 54(1):2-11. doi: 10.5483/BMBRep.2021.54.1.229 [19] Gorvel L, Olive D. Targeting the “PVR–TIGIT axis” with immune checkpoint therapies[J]. F1000Res, 2020, 9: F1000 Faculty Rev-354. [20] Martinet L, Smyth MJ. Balancing natural killer cell activation through paired receptors[J]. Nat Rev Immunol, 2015, 15(4):243-254. doi: 10.1038/nri3799 [21] Zhang Z, Wu N, Lu Y, et al. DNAM-1 controls NK cell activation via an ITT-like motif[J]. J Exp Med, 2015, 212(12):2165-2182. doi: 10.1084/jem.20150792 [22] Braun M, Aguilera AR, Sundarrajan A, et al. CD155 on tumor cells drives resistance to immunotherapy by inducing the degradation of the activating receptor CD226 in CD8+T cells[J]. Immunity, 2020, 53(4):805-823. doi: 10.1016/j.immuni.2020.09.010 [23] Okumura G, Iguchi-Manaka A, Murata R, et al. Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells[J]. J Exp Med, 2020, 217(4):1. [24] Chung W, Eum HH, Lee HO, et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer[J]. Nat Commun, 2017, 8:15081. doi: 10.1038/ncomms15081 [25] Harjunpää H, Guillerey C. TIGIT as an emerging immune checkpoint[J]. Clin Exp Immunol, 2020, 200(2):108-119. doi: 10.1111/cei.13407 [26] Liu S, Zhang H, Li M, et al. Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells[J]. Cell Death Differ, 2013, 20(3):456-464. doi: 10.1038/cdd.2012.141 [27] Horvath L, Pircher A. ASCO 2020 non-small lung cancer (NSCLC) personal highlights[J]. Memo, 2021:1-4. [28] Georgiev H, Ravens I, Papadogianni G, et al. Coming of age: CD96 emerges as modulator of immune responses[J]. Front Immunol, 2018, 9:1072. doi: 10.3389/fimmu.2018.01072 [29] Lepletier A, Lutzky VP, Mittal D, et al. The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells[J]. Immunol Cell Biol, 2019, 97(2):152-164. doi: 10.1111/imcb.12205 [30] Mittal D, Lepletier A, Madore J, et al. CD96 is an immune checkpoint that regulates CD8+ T-cell antitumor function[J]. Cancer Immunol Res, 2019, 7(4):559-571. doi: 10.1158/2326-6066.CIR-18-0637 [31] Sun H, Huang Q, Huang M, et al. Human CD96 correlates to natural killer cell exhaustion and predicts the prognosis of human hepatocellular carcinoma[J]. Hepatology,2019,70(1): 168-183. [32] Poh A. COM701 shows antitumor activity, +/− Nivolumab[J]. Cancer Discov, 2020, 10(6): 752. -
点击查看大图
表(1)
计量
- 文章访问数: 227
- HTML全文浏览量: 98
- PDF下载量: 45
- 被引次数: 0
