Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China.
Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Sci China Life Sci. 2022 Sep;65(9):1824-1839. doi: 10.1007/s11427-021-2078-6. Epub 2022 Apr 29.
Signal transducers and activators of transcription 5 (Stat5) is known to engage in regulating the differentiation and effector function of various subsets of T helper cells. However, how Stat5 regulates the antitumor activity of tumor-infiltrating CD4 T cells is largely unknown. Here, we showed that mice with specific deletion of Stat5 in CD4 T cells were less susceptible to developing subcutaneous and lung metastatic B16 melanoma with CD4 tumor-infiltrating lymphocytes (TILs) remolding. Especially, we confirmed that Stat5-deficient CD4 naïve T cells were prone to polarization of two subtypes of Th17 cells: IFN-γ and IFN-γ Th17 cells, which exhibited increased anti-melanoma activity through enhanced activation of Notch1 pathway compared with wild type Th17 cells. Our study therefore revealed a novel function of Stat5 in regulating tumor-specific Th17 cell differentiation and function in melanoma. This study also provided a new possibility for targeting Stat5 and other Th17-associated pathways to develop novel immunotherapies for melanoma patients.
信号转导子和转录激活子 5（Stat5）已知参与调节各种辅助性 T 细胞亚群的分化和效应功能。然而，Stat5 如何调节肿瘤浸润 CD4 T 细胞的抗肿瘤活性在很大程度上尚不清楚。在这里，我们表明，CD4 T 细胞中特异性缺失 Stat5 的小鼠不易发展成具有 CD4 肿瘤浸润淋巴细胞（TIL）重塑的皮下和肺转移性 B16 黑色素瘤。特别是，我们证实 Stat5 缺陷型 CD4 幼稚 T 细胞易于两种 Th17 细胞亚型的极化：IFN-γ 和 IFN-γ Th17 细胞，与野生型 Th17 细胞相比，通过 Notch1 通路的增强激活，表现出增强的抗黑色素瘤活性。因此，我们的研究揭示了 Stat5 在调节黑色素瘤中肿瘤特异性 Th17 细胞分化和功能中的新功能。这项研究还为靶向 Stat5 和其他 Th17 相关途径以开发黑色素瘤患者的新型免疫疗法提供了新的可能性。
