B cells sustain tumor-specific CD4 T cells to promote response to PD-1 targeted therapy

Abishek Balachandra Vaidya; Étienne Humblin; Nataliya Prokhnevska; Verena van der Heide; Laurine Binet; Jachym Harwood; Raphaël Mattiuz; Anthony Lozano; Pauline Hamon; Bruno Cogliati; Simon Goldstein; Isabel Korpas; Katherine E. Lindblad; Suhaana Sriram; Harald Hartweger; Gláucia Furtado; Sacha Gnjatic; Edgar Gonzalez‐Kozlova; Brad R. Rosenberg; Amaia Lujambio; Miriam Mérad; Michel C. Nussenzweig; Alice Oliffson Kamphorst

doi:10.64898/2026.09.18.751292

ImmunologybioRxivSep 24, 2026

Preprint

B cells sustain tumor-specific CD4 T cells to promote response to PD-1 targeted therapy

Abishek Balachandra Vaidya iD, Étienne Humblin iD, Nataliya Prokhnevska iD, Verena van der Heide iD, Laurine Binet iD, Jachym Harwood iD, Raphaël Mattiuz iD, Anthony Lozano iD, Pauline Hamon iD, Bruno Cogliati iD, Simon Goldstein iD, Isabel Korpas iD, Katherine E. Lindblad iD, Suhaana Sriram iD, Harald Hartweger iD, Gláucia Furtado, Sacha Gnjatic iD, Edgar Gonzalez‐Kozlova iD, Brad R. Rosenberg iD, Amaia Lujambio iD, Miriam Mérad iD, Michel C. Nussenzweig iD, Alice Oliffson Kamphorst iD

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.

PDF DOI