RT Journal Article
SR Electronic
T1 Neoantigen driven B cell and CD4<sup>+</sup> T follicular helper cell collaboration promotes robust anti-tumor CD8<sup>+</sup> T cell responses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.23.424168
DO 10.1101/2020.12.23.424168
A1 Can Cui
A1 Jiawei Wang
A1 Ping-Min Chen
A1 Kelli A. Connolly
A1 Martina Damo
A1 Eric Fagerberg
A1 Shuting Chen
A1 Stephanie C. Eisenbarth
A1 Hongyu Zhao
A1 Joseph Craft
A1 Nikhil S. Joshi
YR 2020
UL http://biorxiv.org/content/early/2020/12/24/2020.12.23.424168.abstract
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.