期刊
CELL
卷 184, 期 25, 页码 6101-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.11.007
关键词
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资金
- NCI [K22CA200912, 1RO1CA237037-01A1]
- NIH [R37AR40072, AR074545]
- Yale SPORE in Lung Cancer [1P50CA196530 1P50CA196530]
- Yale Cancer Center
- Gruber Science Fellowship
- Yale Immunobiology NIH T32 training grant [5T32AI007019]
- Richard K. Gershon Research Fellowship
The study found that the enrichment of TFH cell transcriptional signature in lung adenocarcinoma patients is correlated with GC B cell signature and prolonged survival. Interactions between tumor-specific TFH and GC B cells are crucial for tumor control and effector CD8 T cell function.
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.
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