CTLA4 and melanoma: The recognition of CTLA-4 as a negative regulator of T-cell activation makes antagonizing CTLA-4 a reasonable method to enhance the antitumor immunity of T cells.343 Initial preclinical studies found that CTLA-4 blockade enhanced antitumor immunity and caused regression of immunogenic tumors without inducing substantial autoimmunity.344,345 Based on these preclinical findings, several clinical trials have been conducted to evaluate the therapeutic efficacy of CTLA-4 antibodies in tumors,346–349 which finally led to the FDA approval of ipilimumab by FDA for the treatment of advanced melanoma.