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

Can Cui, Jiawei Wang, Ping-Min Chen, Kelli A. Connolly, Martina Damo, Eric Fagerberg, Shuting Chen, Stephanie C. Eisenbarth, Hongyu Zhao, Joseph Craft, View ORCID ProfileNikhil S. Joshi
doi: https://doi.org/10.1101/2020.12.23.424168
Can Cui
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
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Jiawei Wang
3Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA 06510, USA
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Ping-Min Chen
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
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Kelli A. Connolly
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
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Martina Damo
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
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Eric Fagerberg
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
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Shuting Chen
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
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Stephanie C. Eisenbarth
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
2Department of Internal Medicine (Rheumatology, Allergy and Immunology), Yale University School of Medicine, New Haven, CT 06520, USA
4Department of Lab Medicine, Yale University School of Medicine, New Haven, CT 06519, USA
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Hongyu Zhao
5Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA
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Joseph Craft
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
2Department of Internal Medicine (Rheumatology, Allergy and Immunology), Yale University School of Medicine, New Haven, CT 06520, USA
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Nikhil S. Joshi
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
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  • ORCID record for Nikhil S. Joshi
  • For correspondence: nikhil.joshi@yale.edu
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Abstract

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.

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Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 24, 2020.
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Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses
Can Cui, Jiawei Wang, Ping-Min Chen, Kelli A. Connolly, Martina Damo, Eric Fagerberg, Shuting Chen, Stephanie C. Eisenbarth, Hongyu Zhao, Joseph Craft, Nikhil S. Joshi
bioRxiv 2020.12.23.424168; doi: https://doi.org/10.1101/2020.12.23.424168
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Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses
Can Cui, Jiawei Wang, Ping-Min Chen, Kelli A. Connolly, Martina Damo, Eric Fagerberg, Shuting Chen, Stephanie C. Eisenbarth, Hongyu Zhao, Joseph Craft, Nikhil S. Joshi
bioRxiv 2020.12.23.424168; doi: https://doi.org/10.1101/2020.12.23.424168

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