CTLA4 and neoplasm: Despite extensive immune system activation induced by cetuximab, residual tumor-associated cells can prevent the final attack of cytotoxic T cells on the tumor by upregulation of PD-1, PD-L1, and CTLA-4 on their surface or by releasing cytokines such as TGF-β or chemokines such as CXCL12, which inactivate effector cells (25).