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摘要: 以抗细胞程序性死亡-1/细胞程序性死亡-配体1（programmed cell death-1/programmed cell death-ligand 1，PD-1/PD-L1）为代表的免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）治疗显现了CD8+T细胞在治疗和可能治愈恶性肿瘤方面的潜力。但仅约20%的患者对ICIs治疗获益，因此阐明CD8+T细胞在免疫微环境中的有效抗肿瘤功能，及其分子和空间的决定因素尤为重要。具有自我更新、增殖分化和杀伤肿瘤细胞能力的干细胞样CD8+T细胞亚群，在介导抗肿瘤免疫效应方面扮演极为重要的角色。本文就干细胞样CD8+T细胞在抗肿瘤免疫循环中的地位与演进效应进行综述。
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关键词:
- 干细胞样CD8+T淋巴细胞 /
- 免疫治疗 /
- 肿瘤微环境
Abstract: Anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) as immune checkpoint inhibitors (ICIs) therapy has shown the potential of CD8+T cells in treating and possibly curing malignancies. However, only approximately 20% of patients benefit from ICI therapy. Therefore, it is necessary to elucidate the antitumor function of CD8+T cells in the immune microenvironment and its molecular and spatial mechanism of action. Stem-like CD8+T-cell subsets with the ability of self-renewal, proliferation, differentiation, and killing of tumor cells play a vital role in mediating anti-tumor effects. In this review, we analyzed the roles and evolutionary effects of stem-like CD8+T cells in anti-tumor effects.-
Key words:
- stem-like CD8+T-lymphocytes /
- immunotherapy /
- tumor microenvironment
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[1] Falzone L, Salomone S, Libra M. Evolution of cancer pharmacological treatments at the turn of the third millennium[J]. Front Pharmacol, 2018, 9:1300. doi: 10.3389/fphar.2018.01300 [2] Schoenfeld AJ, Hellmann MD. Acquired resistance to immune checkpoint inhibitors[J]. Cancer Cell, 2020, 37(4):443-455. doi: 10.1016/j.ccell.2020.03.017 [3] Kalbasi A, Ribas A. Tumour-intrinsic resistance to immune checkpoint blockade[J]. Nat Rev Immunol, 2020, 20(1):25-39. doi: 10.1038/s41577-019-0218-4 [4] Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, adaptive, and acquired resistance to cancer immunotherapy[J]. Cell, 2017, 168(4):707-723. [5] Pitt JM, Vétizou M, Daillère R, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: Tumor-intrinsic and -extrinsic factors[J]. Immunity, 2016, 44(6):1255-1269. doi: 10.1016/j.immuni.2016.06.001 [6] Philip M, Schietinger A. CD8+T cell differentiation and dysfunction in cancer[J]. Nat Rev Immunol, 2022, 22(4):209-223. doi: 10.1038/s41577-021-00574-3 [7] Scott AC, Dündar F, Zumbo P, et al. Tox is a critical regulator of tumour-specific t cell differentiation[J]. Nature, 2019, 571(7764):270-274. doi: 10.1038/s41586-019-1324-y [8] Khan O, Giles JR, McDonald S, et al. Tox transcriptionally and epigenetically programs cd8(+) t cell exhaustion[J]. Nature, 2019, 571(7764):211-218. [9] Yost KE, Satpathy AT, Wells DK, et al. Clonal replacement of tumor-specific t cells following pd-1 blockade[J]. Nat Med, 2019, 25(8):1251-1259. [10] Connolly KA, Kuchroo M, Venkat A, et al. A reservoir of stem-like CD8+T cells in the tumor-draining lymph node preserves the ongoing antitumor immune response[J]. Sci Immunol, 2021, 6(64):eabg7836. [11] Gearty SV, Dündar F, Zumbo P, et al. An autoimmune stem-like CD8+T cell population drives type 1 diabetes[J]. Nature, 2022, 602(7895):156-161. [12] Krishna S, Lowery FJ, Copeland AR, et al. Stem-like cd8 t cells mediate response of adoptive cell immunotherapy against human cancer[J]. Science, 2020, 370(6522):1328-1334. doi: 10.1126/science.abb9847 [13] Galletti G, De Simone G, Mazza EMC, et al. Two subsets of stem-like CD8+ memory t cell progenitors with distinct fate commitments in humans[J]. Nat Immunol, 2020, 21(12):1552-1562. doi: 10.1038/s41590-020-0791-5 [14] Garris CS, Arlauckas SP, Kohler RH, et al. Successful anti-pd-1 cancer immunotherapy requires t cell-dendritic cell crosstalk involving the cytokines ifn-γ and il-12[J]. Immunity, 2018, 49(6):1148-1161. [15] Li Z, Tuong ZK, Dean I, et al. In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue[J]. J Exp Med, 2022, 219(6): e20210749. [16] Rutishauser RL, Martins GA, Kalachikov S, et al. Transcriptional repressor blimp-1 promotes cd8(+) t cell terminal differentiation and represses the acquisition of central memory t cell properties[J]. Immunity, 2009, 31(2):296-308. [17] Siddiqui I, Schaeuble K, Chennupati V, et al. Intratumoral TCF1(+)PD-1(+)CD8(+) t cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy[J]. Immunity, 2019, 50(1):195-211. [18] Bangs DJ, Tsitsiklis A, Steier Z, et al. Cxcr3 regulates stem and proliferative CD8+ T cells during chronic infection by promoting interactions with DCS in splenic bridging channels[J]. Cell Rep, 2022, 38(3):110266. doi: 10.1016/j.celrep.2021.110266 [19] Buchholz VR, Busch DH. Back to the future: effector fate during t cell exhaustion[J]. Immunity, 2019, 51(6):970-972. doi: 10.1016/j.immuni.2019.11.007 [20] Yi L, Yang L. Stem-like t cells and niches: Implications in human health and disease[J]. Front Immunol, 2022, 13:907172. doi: 10.3389/fimmu.2022.907172 [21] Wieland D, Kemming J, Schuch A, et al. TCF1(+) hepatitis c virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulation[J]. Nat Commun, 2017, 8:15050. doi: 10.1038/ncomms15050 [22] Feng Q, Liu Z, Yu X, et al. Lactate increases stemness of CD8+ T cells to augment anti-tumor immunity[J]. Nat Commun, 2022, 13(1):4981. doi: 10.1038/s41467-022-32521-8 [23] Wu T, Ji Y, Moseman EA, et al. The tcf1-bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness[J]. Sci Immunol, 2016, 1(6):eaai8593. [24] Zhao X, Shan Q, Xue HH. TCF1 in T cell immunity: A broadened frontier[J]. Nat Rev Immunol, 2022, 22(3):147-157. doi: 10.1038/s41577-021-00563-6 [25] Chan JD, Lai J, Slaney CY, et al. Cellular networks controlling T cell persistence in adoptive cell therapy[J]. Nat Rev Immunol, 2021, 21(12):769-784. doi: 10.1038/s41577-021-00539-6 [26] Crespo J, Sun H, Welling TH, et al. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment[J]. Curr Opin Immunol, 2013, 25(2):214-221. doi: 10.1016/j.coi.2012.12.003 [27] Hudson WH, Gensheimer J, Hashimoto M, et al. Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1(+) stem-like CD8+ T cells during chronic infection[J]. Immunity, 2019, 51(6):1043-1058. doi: 10.1016/j.immuni.2019.11.002 [28] Kanev K, Wu M, Drews A, et al. Proliferation-competent TCF1+ CD8 T cells in dysfunctional populations are CD4 T cell help independent[J]. Proc Natl Acad Sci U S A, 2019, 116(40):20070-20076. doi: 10.1073/pnas.1902701116 [29] Chen CY, Ueha S, Ishiwata Y, et al. Combining an alarmin hmgn1 peptide with PD-l1 blockade results in robust antitumor effects with a concomitant increase of stem-like/progenitor exhaustedCD8+ T cells[J]. Cancer Immunol Res, 2021, 9(10):1214-1228. doi: 10.1158/2326-6066.CIR-21-0265 [30] Gaudreau PO, Negrao MV, Mitchell KG, et al. Neoadjuvant chemotherapy increases cytotoxic T cell, tissue resident memory T cell, and B cell infiltration in resectable nsclc[J]. J Thorac Oncol, 2021, 16(1):127-139. doi: 10.1016/j.jtho.2020.09.027 [31] Huang Q, Wu X, Wang Z, et al. The primordial differentiation of tumor-specific memory CD8+T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes[J]. Cell, 2022, 185(22):4049-4066. [32] Heuser C, Gattinoni L. C-myb redefines the hierarchy of stem-like T cells[J]. Nat Immunol, 2022, 23(10):1405-1407. doi: 10.1038/s41590-022-01319-7 [33] Jansen CS, Prokhnevska N, Master VA, et al. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells[J]. Nature, 2019, 576(7787):465-470. doi: 10.1038/s41586-019-1836-5 -
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