Revisiting T Cell Tolerance as a Checkpoint Target for Cancer Immunotherapy.
Revisiting T Cell Tolerance as a Checkpoint Target for Cancer Immunotherapy.
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DOI：
10.3389/fimmu.2020.589641
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发表时间：
2020
影响因子：
7.3
通讯作者：
Parish IA
中科院分区：
文献类型：
--
作者：
Nüssing S;Trapani JA;Parish IA
免疫疗法彻底改变了癌症的治疗方法。然而，大多数患者对治疗没有反应，这意味着需要更深入地了解肿瘤免疫逃避策略，以提高治疗效果。绝大多数免疫治疗研究都集中在治疗如何重振肿瘤内耗尽的CD8+T细胞。相比之下，治疗如何影响引流淋巴结内的调节过程的研究较少。特别是，在研究肿瘤如何利用外周CD8+T细胞耐受方面做的相对较少，CD8+T细胞耐受是一种研究不足的免疫检查点，在正常情况下通过阻止T细胞反应的启动来预防有害的自身免疫性疾病。在这里，我们回顾了阻断外周CD8+T细胞耐受治疗癌症的可能性。我们首先全面回顾了从首次定义外周耐受的非肿瘤模型中了解到的CD8+T细胞外周耐受的调节。接下来，我们考虑耐受状态与其他负调节状态的不同之处，例如T细胞耗尽和衰老。最后，我们描述了肿瘤如何劫持外周耐受免疫检查点以防止抗肿瘤免疫反应，并认为外周耐受的破坏可能有助于免疫治疗的抗癌疗效和自身免疫副作用。总体而言，我们认为，加深对外周免疫耐受的理解，最终将有助于开发更有针对性和更精细的癌症免疫治疗方法。
Immunotherapy has revolutionized the treatment of cancer. Nevertheless, the majority of patients do not respond to therapy, meaning a deeper understanding of tumor immune evasion strategies is required to boost treatment efficacy. The vast majority of immunotherapy studies have focused on how treatment reinvigorates exhausted CD8+ T cells within the tumor. In contrast, how therapies influence regulatory processes within the draining lymph node is less well studied. In particular, relatively little has been done to examine how tumors may exploit peripheral CD8+ T cell tolerance, an under-studied immune checkpoint that under normal circumstances prevents detrimental autoimmune disease by blocking the initiation of T cell responses. Here we review the therapeutic potential of blocking peripheral CD8+ T cell tolerance for the treatment of cancer. We first comprehensively review what has been learnt about the regulation of CD8+ T cell peripheral tolerance from the non-tumor models in which peripheral tolerance was first defined. We next consider how the tolerant state differs from other states of negative regulation, such as T cell exhaustion and senescence. Finally, we describe how tumors hijack the peripheral tolerance immune checkpoint to prevent anti-tumor immune responses, and argue that disruption of peripheral tolerance may contribute to both the anti-cancer efficacy and autoimmune side-effects of immunotherapy. Overall, we propose that a deeper understanding of peripheral tolerance will ultimately enable the development of more targeted and refined cancer immunotherapy approaches.
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DOI：
10.1084/jem.187.10.1555
发表时间：
1998-05-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Adler AJ;Marsh DW;Yochum GS;Guzzo JL;Nigam A;Nelson WG;Pardoll DM
通讯作者：
Pardoll DM
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.
DOI：
10.1073/pnas.0408197102
发表时间：
2005-01-11
影响因子：
11.1
作者：
Chen, ML;Pittet, MJ;Khazaie, K
通讯作者：
Khazaie, K
CD8α(+)树突状细胞负责诱导外周组织相关抗原的自身耐受。
影响因子：
15.3
作者：
Belz, Gabrielle T;Behrens, Georg M N;Smith, Chris M;Miller, Jacques F A P;Jones, Claerwen;Lejon, Kristina;Fathman, C Garrison;Mueller, Scott N;Shortman, Ken;Carbone, Francis R;Heath, William R
通讯作者：
Heath, William R
影响因子：
32.4
作者：
Boissonnas, Alexandre;Scholer-Dahirel, Alix;Amigorena, Sebastian
通讯作者：
Amigorena, Sebastian