CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours

Abstract Most clinically applied cancer immunotherapies rely on the ability of CD8 + cytolytic T cells to directly recognize and kill tumour cells 1–3 . These strategies are limited by the emergence of major histocompatibility complex (MHC)-deficient tumour cells and the formation of an immunosuppressive tumour microenvironment 4–6 . The ability of CD4 + effector cells to contribute to antitumour immunity independently of CD8 + T cells is increasingly recognized, but strategies to unleash their full potential remain to be identified 7–10 . Here, we describe a mechanism whereby a small number of CD4 + T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8 + T cell targeting. The CD4 +…