The second molecular roadblock to ICIs in GI cancers is the deficient cancer antigen presentation through MHC downregulation.[46] Constitutively, active oncogenes such as mutant KRAS downregulate MHC expression effectively, impeding tumor-associated antigen presentation.[47] Thus, strategies to increase the presentation of existing neoantigens through modulating MHC expression or enhancing the ability of antigen-presenting cells (APCs) to activate T cells could be of greatly benefit. This evidence concerns the gene HLA-C and cancer.