Several factors, including lack of tumor antigen presentation, low TMB, absence of infiltrating T cells (“Cold tumors”), inhibitory immune checkpoints beyond PD-1/PD-L1 and CTLA-4, or immunosuppressive cytokines, can lead to intrinsic (primary) resistance, which exists before the start of treatment and prevents the therapy from being effective at all [60,61]. This evidence concerns the gene CTLA4 and neoplasm.