CTLA4 and cancer: CTLA-4-mediated coinhibitory signaling is critical for negative regulation of T cell activation and proliferation, as evidenced by the severe lymphoproliferation and multi-organ inflammatory lymphocytic infiltrates observed in mice lacking CTLA-4 signaling (Tivol et al., 1995) or in cancer patients receiving anti-CTLA-4 antibodies (Pardoll, 2012).