Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses

Can Cui, Jiawei Wang, Eric Fagerberg, Ping Min Chen, Kelli A. Connolly, Martina Damo, Julie F. Cheung, Tianyang Mao, Adnan S. Askari, Shuting Chen, Brittany Fitzgerald, Gena G. Foster, Stephanie C. Eisenbarth, Hongyu Zhao, Joseph Craft*, Nikhil S. Joshi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6101-6118.e13
Issue number25
StatePublished - Dec 9 2021
Externally publishedYes


  • B cell
  • CD8 T cell
  • IL-21
  • T follicular helper cell
  • lung cancer
  • neoantigen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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