B cells sustain tumor-specific CD4 T cells to promote response to PD-1 targeted therapy
Vaidya, A.; Humblin, E.; Prokhnevska, N.; van der Heide, V.; Binet, L.; Harwood, J.; Mattiuz, R.; Lozano, A.; Hamon, P.; Cogliati, B.; Goldstein, S.; Korpas, I.; Lindblad, K. E.; Sriram, S.; Hartweger, H.; Furtado, G.; Gnjatic, S.; Gonzalez-Kozlova, E.; Rosenberg, B. R.; Lujambio, A.; Merad, M.; Nussenzweig, M. C.; Kamphorst, A. O.
Show 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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