Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06510, USA.
Cell. 2021 Dec 9;184(25):6101-6118.e13. doi: 10.1016/j.cell.2021.11.007. Epub 2021 Nov 30.
CD4 T follicular helper (TFH) cells support B cells, which are critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found enrichment of TFH cell transcriptional signature correlates with GC B cell signature and with prolonged survival in individuals with lung adenocarcinoma (LUAD). We further developed a murine LUAD model in which tumor cells express B cell- and T cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells, as well as interleukin (IL)-21 primarily produced by TFH cells, are necessary for tumor control and effector CD8 T cell function. Development of TFH cells requires B cells and B cell-recognized neoantigens. Thus, tumor neoantigens can regulate the fate of tumor-specific CD4 T cells by facilitating their interactions with tumor-specific B cells, which in turn promote anti-tumor immunity by enhancing CD8 T cell effector functions.
CD4+滤泡辅助性 T 细胞（TFH）支持 B 细胞，B 细胞对生发中心（GC）的形成至关重要，但 TFH-B 细胞相互作用在癌症中的重要性尚不清楚。我们发现 TFH 细胞转录特征的富集与 GC B 细胞特征以及肺腺癌（LUAD）患者的生存时间延长相关。我们进一步开发了一种小鼠 LUAD 模型，其中肿瘤细胞表达 B 细胞和 T 细胞识别的新抗原。肿瘤特异性 TFH 与 GC B 细胞之间的相互作用，以及主要由 TFH 细胞产生的白细胞介素（IL）-21，是肿瘤控制和效应 CD8 T 细胞功能所必需的。TFH 细胞的发育需要 B 细胞和 B 细胞识别的新抗原。因此，肿瘤新抗原可以通过促进其与肿瘤特异性 B 细胞的相互作用来调节肿瘤特异性 CD4 T 细胞的命运，进而通过增强 CD8 T 细胞效应功能来促进抗肿瘤免疫。
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