Abstract
CD4+ T helper cells play an important role in adoptive T cell therapy (ACT) success, but it remains unclear which subset is most therapeutic and how they eliminate tumors. We find that tumor-specific Th17 cells eradicate melanoma more effectively than other CD4+ subsets and protect against distant metastases by unique orchestration of host immunity. Donor Th17 cells require host B cells -but not T cells- for tumor regression. Th17 cells induce B cell proliferation, activation, and differentiation, while B cells augment Th17 cell polyfunctionality by enhancing IL-21 production. Th17 and B cells colocalize in lymphoid tissues, where Th17 cells induce germinal centers and tumor-reactive antibodies via IL-21 production and CD40L costimulation. Furthermore, these tumor-specific antibodies provide partial protection against tumor challenge. Herein, we reveal that adoptively transferred Th17 cells cooperate with B cells to drive sustained immunity, demonstrating a role for endogenous B cell responses in effective CD4+ ACT.