However, the mechanisms underlying irAE development are less clear, with 4 processes tentatively described: (1) increasing T-cell activity against antigens shared by tumor cells and healthy tissue; (2) accumulating levels of preexisting host autoantibodies; (3) rising levels of inflammatory cytokines; and (4) direct binding of anti–CTLA-4 antibodies with CTLA-4 found on healthy tissue, intensifying complement-mediated inflammation. This evidence concerns the gene CTLA4 and neoplasm.