CXCR6+ T cells are required for CD3xCD20 Bispecific Antibody Efficacy in B cell Lymphomas

Activation of endogenous T cells using bispecific antibodies targeting CD3 and CD20 (BsAb) has emerged as a promising strategy for patients with B cell lymphomas. However, T cell features associated with treatment response or resistance are poorly understood. Here we identify an essential role for cytotoxic T cells in mediating response to BsAb in B cell lymphomas. In a disseminated B cell lymphoma model, BsAb showed substantial anti-tumor efficacy, which was dependent on activation and expansion of CD8+ T cells. Analysis of primary tumor samples from BsAb-treated patients confirmed that CD8+ T cell abundance was associated with durable remission and identified CXCR6+ cytotoxic T cells as associated with complete response. Cxcr6 knockout abrogated BsAb efficacy despite activation of CD4+ and CD8+ T cells. These results link BsAb efficacy to tumor resident cytotoxic T cells and suggest that enhancing chemokine-dependent T cell recruitment may augment therapeutic efficacy.