Department of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Research Center of Digital Medicine, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Mol Immunol. 2022 Apr;144:117-126. doi: 10.1016/j.molimm.2022.02.005. Epub 2022 Feb 23.
Id3, an inhibitor of DNA binding protein, plays important roles in the function and homeostasis of effector and memory T cells. Recent evidence has shown that Id3 is also implicated in CD8 T cell exhaustion. However, whether and how Id3 might regulate effector function or exhaustion of CD8 T cells, especially in the tumor setting, is still unknown. Here, we first showed that Id3 expression was impaired in tumor-infiltrating CD8 T cells as liver cancer progressed, especially in PD-1 +Tim-3 + exhausted CD8 T cells. Enforced expression of Id3 in CD8 T cells resulted in repressed development of anti-tumor CTLs exhaustion, which offered better tumor control. And partially depletion of Id3 in CD8 T cells promoted the development of exhausted CD8 T cells. Furthermore, Id3hi CD8 T cells could respond to PD-1 blockade. Collectively, Id3 exerts protective functions in CD8 T cells for liver cancer.
Id3 是 DNA 结合蛋白抑制剂，在效应器和记忆 T 细胞的功能和稳态中发挥重要作用。最近的证据表明，Id3 也与 CD8 T 细胞耗竭有关。然而，Id3 是否以及如何调节 CD8 T 细胞的效应功能或耗竭，特别是在肿瘤环境中，仍然未知。在这里，我们首先表明，随着肝癌的进展，肿瘤浸润 CD8 T 细胞中 Id3 的表达受损，特别是在 PD-1+Tim-3+耗尽的 CD8 T 细胞中。在 CD8 T 细胞中强制表达 Id3 会抑制抗肿瘤 CTL 耗竭的发展，从而更好地控制肿瘤。而 CD8 T 细胞中 Id3 的部分耗竭则促进了耗竭 CD8 T 细胞的发展。此外，Id3hi CD8 T 细胞可以对 PD-1 阻断作出反应。总之，Id3 对肝癌 CD8 T 细胞具有保护作用。
