CD8⁺ T cells specific for cancer cells are detected within tumours. However, despite their presence, tumours progress. The clinical success of immune checkpoint blockade and adoptive T cell therapy demonstrates the potential of CD8⁺ T cells to mediate antitumour responses; however, most patients with cancer fail to achieve long-term responses to immunotherapy. Here we review CD8⁺ T cell differentiation to dysfunctional states during tumorigenesis. We highlight similarities and differences between T cell dysfunction and other hyporesponsive T cell states and discuss the spatio-temporal factors contributing to T cell state heterogeneity in tumours. An important challenge is predicting which patients will respond to immunotherapeutic interventions and understanding which T cell subsets mediate the clinical response. We explore our current understanding of what determines T cell responsiveness and resistance to immunotherapy and point out the outstanding research questions.

在肿瘤内检测到癌细胞特异性的CD8 ^{+ T 细胞。}然而，尽管它们存在，肿瘤仍在进展。免疫检查点阻断和过继性 T 细胞疗法的临床成功证明了 CD8 ⁺ T 细胞介导抗肿瘤反应的潜力；然而，大多数癌症患者无法对免疫疗法产生长期反应。下面我们回顾一下CD8 ⁺T 细胞在肿瘤发生过程中分化为功能失调状态。我们强调了 T 细胞功能障碍和其他低反应性 T 细胞状态之间的异同，并讨论了导致肿瘤中 T 细胞状态异质性的时空因素。一个重要的挑战是预测哪些患者会对免疫治疗干预产生反应，并了解哪些 T 细胞亚群介导临床反应。我们探讨了我们目前对什么决定了 T 细胞对免疫疗法的反应性和耐药性的理解，并指出了悬而未决的研究问题。