@article{2cc90aa883f94ce5b6e646b6859dd0ca,
title = "Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses",
abstract = "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.",
keywords = "B cell, CD8 T cell, IL-21, T follicular helper cell, lung cancer, neoantigen",
author = "Can Cui and Jiawei Wang and Eric Fagerberg and Chen, {Ping Min} and Connolly, {Kelli A.} and Martina Damo and Cheung, {Julie F.} and Tianyang Mao and Askari, {Adnan S.} and Shuting Chen and Brittany Fitzgerald and Foster, {Gena G.} and Eisenbarth, {Stephanie C.} and Hongyu Zhao and Joseph Craft and Joshi, {Nikhil S.}",
note = "Funding Information: We thank the N.S.J. and J.C. laboratory members for reviewing the manuscript; Z. Chen, C. Yang, and N. Ruddle for helpful discussions; and W. Wei for important guidance on statistical analysis. We also thank the Yale Flow Cytometry Core, Yale Keck DNA Sequencing Facility, Yale School of Medicine Histology Facility, and NIH Tetramer Core Facility. SW HEL mice were kindly provided by Dr. Robert Brink. Figures 2 A, S4 B, S6 A, and S6B and the graphical abstract were created with https://www.biorender.com . This work was supported by grants from the NCI ( K22CA200912 and 1RO1CA237037-01A1 to N.S.J.), NIH ( R37AR40072 and AR074545 to J.C.), and Yale SPORE in Lung Cancer (1P50CA196530 1P50CA196530 to N.S.J. and J.C.) and a Pilot Grant from Yale Cancer Center (to N.S.J. and J.C.). C.C. was supported by the Gruber Science Fellowship and Richard K. Gershon Research Fellowship. J.F.C., K.A.C., and B.F. were supported by the Yale Immunobiology NIH T32 training grant ( 5T32AI007019 ). Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = dec,
day = "9",
doi = "10.1016/j.cell.2021.11.007",
language = "English (US)",
volume = "184",
pages = "6101--6118.e13",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "25",
}
