Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Journal
Cell
Journal Volume
184
Journal Issue
25
Pages
6101
Date Issued
2021-12-09
Author(s)
Cui, Can
Wang, Jiawei
Fagerberg, Eric
Connolly, Kelli A
Damo, Martina
Cheung, Julie F
Mao, Tianyang
Askari, Adnan S
Chen, Shuting
Fitzgerald, Brittany
Foster, Gena G
Eisenbarth, Stephanie C
Zhao, Hongyu
Craft, Joseph
Joshi, Nikhil S
Abstract
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.
Subjects
B cell; CD8 T cell; IL-21; T follicular helper cell; lung cancer; neoantigen
SDGs
Publisher
CELL PRESS
Type
journal article