More importantly, by using different genetic models and therapeutic anti-CTLA-4 mAbs, we show that irAE and CITE are not intrinsically linked and they have a distinct genetic and immunological basis, as complete CTLA-4 occupation, systemic T cell activation and preferential expansion of self-reactive T cells are dispensable for tumor rejection but correlate with irAE. This evidence concerns the gene CTLA4 and neoplasm.