Abstract

Tumor-infiltrating CD8 T cells are associated with improved patient survival and response to immunotherapy in various cancers. Persistent antigen leads to CD8 T-cell exhaustion, where proliferation/self-renewal and killing are divided within distinct subsets of CD8 T cells in the tumor. CD8 T-cell responses in chronic antigen settings must be maintained for long periods of time, suggesting that mechanisms that regulate chronic CD8 T-cell responses may differ from those in acute settings. Currently, factors that regulate the maintenance of stem-like CD8 T cells in the tumor or their differentiation into terminally differentiated cells are unknown. In this review, we discuss the role of dendritic cells in the activation and differentiation of CD8 T-cell subsets within secondary lymphoid tissue and tumors. In addition, we examine changes in CD4 T-cell differentiation in response to chronic antigens and consider how subset-specific mechanisms could assist the stem-like and terminally differentiated CD8 T-cell subsets. Finally, we highlight how tumor-infiltrating CD4 T cells and dendritic cells interact with CD8 T cells within organized lymphoid-like areas in the tumor and propose a CD8 T-cell differentiation model that requires the collaboration of CD4 T cells and dendritic cells. These organized interactions coordinate the anti-tumor response and control disease progression by mechanisms that regulate CD8 T-cell differentiation, which permit the maintenance of an effective balance of stem-like and terminally differentiated CD8 T cells.

中文翻译：

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肿瘤内有组织的免疫细胞相互作用维持生产性 T 细胞反应。

摘要

肿瘤浸润性 CD8 T 细胞与改善患者生存率和对各种癌症的免疫治疗反应有关。持久性抗原导致 CD8 T 细胞耗竭，其中增殖/自我更新和杀伤被划分为肿瘤中不同的 CD8 T 细胞亚群。慢性抗原环境中的 CD8 T 细胞反应必须长期维持，这表明调节慢性 CD8 T 细胞反应的机制可能与急性环境中的机制不同。目前，调节肿瘤中干细胞样 CD8 T 细胞维持或分化为终末分化细胞的因素尚不清楚。在这篇综述中，我们讨论了树突状细胞在次级淋巴组织和肿瘤内 CD8 T 细胞亚群的激活和分化中的作用。此外，我们检查了响应慢性抗原的 CD4 T 细胞分化的变化，并考虑了亚群特异性机制如何帮助干细胞样和终末分化的 CD8 T 细胞亚群。最后，我们强调了肿瘤浸润性 CD4 T 细胞和树突细胞如何与肿瘤组织淋巴样区域内的 CD8 T 细胞相互作用，并提出了一个需要 CD4 T 细胞和树突细胞协作的 CD8 T 细胞分化模型。这些有组织的相互作用通过调节 CD8 T 细胞分化的机制来协调抗肿瘤反应和控制疾病进展，这允许维持干细胞样和终末分化的 CD8 T 细胞的有效平衡。