The rationales behind these combinations are multifactorial and include activating T cells by regulating different signaling pathways (the CTLA-4 checkpoint is critical for T cell priming and activation, whereas PD-1 blocks effector T cell responses in tissues), enhancing tumor antigen expression, exposing more new antigen mutations and higher mutation burdens, inducing PD-L1 expression, augmenting T cell infiltration around the metastatic sites, and producing a more favorable tumor microenvironment [1, 41]. Here, CTLA4 is linked to neoplasm.