B cells sustain tumor-specific CD4 T cells to promote response to PD-1 targeted therapy
- 1Icahn School of Medicine at Mount Sinai
Abstract
Immunotherapy transformed cancer treatment, yet precise correlates of response remain to be defined. While intratumoral follicular helper like (Tfhl) CD4 T cells and IgG1+ B cells have been associated with improved outcomes to PD-1 blockade for hepatocellular carcinoma (HCC), their mechanisms contributing to response are unclear. To address this question, we developed a murine model of HCC and examined CD8, CD4 and B cell responses. Increasing CD4-help sensitizes mice to PD-1 blockade, in a CD4- and CD8-dependent manner. Tumor-specific CD4 T cells contained Tfhl and Th1 populations, and both Bcl6 and T-bet were required for efficacy. Antigen-specific B cells were essential for CD4-helper expansion, yet secretion of antibodies was not required for long-term survival. Thus, B cells are critical for effective immunotherapy, but secreted antibodies are not.
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BibTeX
@misc{vaidya2026cells,
title = {{B cells sustain tumor-specific CD4 T cells to promote response to PD-1 targeted therapy}},
author = {A. Vaidya and E. Humblin and N. Prokhnevska and V. van der Heide and L. Binet and J. Harwood and R. Mattiuz and A. Lozano and P. Hamon and B. Cogliati and S. Goldstein and I. Korpas and K. E. Lindblad and S. Sriram and H. Hartweger and G. Furtado and S. Gnjatic and E. Gonzalez-Kozlova and B. R. Rosenberg and A. Lujambio and M. Merad and M. C. Nussenzweig and A. O. Kamphorst},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.751292},
url = {https://www.biorxiv.org/content/10.64898/2026.09.18.751292v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - B cells sustain tumor-specific CD4 T cells to promote response to PD-1 targeted therapy
AU - A. Vaidya
AU - E. Humblin
AU - N. Prokhnevska
AU - V. van der Heide
AU - L. Binet
AU - J. Harwood
AU - R. Mattiuz
AU - A. Lozano
AU - P. Hamon
AU - B. Cogliati
AU - S. Goldstein
AU - I. Korpas
AU - K. E. Lindblad
AU - S. Sriram
AU - H. Hartweger
AU - G. Furtado
AU - S. Gnjatic
AU - E. Gonzalez-Kozlova
AU - B. R. Rosenberg
AU - A. Lujambio
AU - M. Merad
AU - M. C. Nussenzweig
AU - A. O. Kamphorst
PY - 2026
DA - 2026/09/18
PB - bioRxiv
DO - 10.64898/2026.09.18.751292
UR - https://www.biorxiv.org/content/10.64898/2026.09.18.751292v1
AB - Immunotherapy transformed cancer treatment, yet precise correlates of response remain to be defined. While intratumoral follicular helper like (Tfhl) CD4 T cells and IgG1+ B cells have been associated with improved outcomes to PD-1 blockade for hepatocellular carcinoma (HCC), their mechanisms contributing to response are unclear. To address this question, we developed a murine model of HCC and examined CD8, CD4 and B cell responses. Increasing CD4-help sensitizes mice to PD-1 blockade, in a CD4- and CD8-dependent manner. Tumor-specific CD4 T cells contained Tfhl and Th1 populations, and both Bcl6 and T-bet were required for efficacy. Antigen-specific B cells were essential for CD4-helper expansion, yet secretion of antibodies was not required for long-term survival. Thus, B cells are critical for effective immunotherapy, but secreted antibodies are not.
ER -