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

Autor: Eric Fagerberg, Stephanie C. Eisenbarth, Joe Craft, Ping-Min Chen, Can Cui, Martina Damo, Hongyu Zhao, Kelli A. Connolly, Jiawei Wang, Shuting Chen, Nikhil S. Joshi
Rok vydání: 2020
Předmět:
Popis: 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.Abstract Figure
Databáze: OpenAIRE