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 T 滤泡辅助 (TFH) 细胞支持 B 细胞，这对生发中心 (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 细胞特征相关，并与肺腺癌 (LUAD) 患者的生存期延长相关。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 和 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，