PT  - JOURNAL ARTICLE
AU  - Can Cui
AU  - Jiawei Wang
AU  - Ping-Min Chen
AU  - Kelli A. Connolly
AU  - Martina Damo
AU  - Eric Fagerberg
AU  - Shuting Chen
AU  - Stephanie C. Eisenbarth
AU  - Hongyu Zhao
AU  - Joseph Craft
AU  - Nikhil S. Joshi
TI  - Neoantigen driven B cell and CD4<sup>+</sup> T follicular helper cell collaboration promotes robust anti-tumor CD8<sup>+</sup> T cell responses
AID  - 10.1101/2020.12.23.424168
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.23.424168
4099  - http://biorxiv.org/content/early/2020/12/24/2020.12.23.424168.short
4100  - http://biorxiv.org/content/early/2020/12/24/2020.12.23.424168.full
AB  - CD4+ T follicular helper (TFH) cells provide help to B cells, which is critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found TFH cells correlated with GC B cells and with prolonged survival of lung adenocarcinoma (LUAD) patients. To investigate further, we developed an LUAD model, in which tumor cells expressed B-cell- and T-cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells were necessary for tumor control, as were effector CD8+ T cells. The latter were reduced in the absence of T cell-B cell interactions or the IL-21 receptor. IL-21 was produced primarily by TFH cells, development of which required B cells. Moreover, development of tumor-specific TFH cell-responses was also reliant upon tumors that expressed B-cell-recognized neoantigens. Thus, tumor-neoantigens themselves can control the fate decisions of tumor-specific CD4+ T cells by facilitating interactions with tumor-specific B cells.Competing Interest StatementThe authors have declared no competing interest.