CTLA4 and neoplasm: We hypothesized that autocrine and paracrine TGFβ signaling in the localized microenvironment of tumor-infiltrating T cells could skew them toward Tregs and attenuate the activation of TH1 and CD8+ immune effector cells, thereby limiting the therapeutic efficacy of CTLA-4 or PD-1/PD-L1 antagonists44,45.