CD4 and neoplasm: The production of IFN-γ, TNF-α and granzyme B by the CD8+ TILs was significantly reduced in B16-3340 tumors of CD4 depleted mice compared to that of cells from control (non-CD4 depleted) mice, consistent with a critical role for microbiota-dependent CD4+ T cell help in the maturation and function of cytotoxic T cells within the tumor microenvironment (Extended Data Fig. 4c–e).