The recognition of neoantigens and activation of T cells can also be compromised by immunosuppressive TME processes, including the suppression of immunological checkpoints, the immunosuppressive effects of various TME cells, and the release of ions or proteins from within tumor cells following necrosis.245 The immunosuppressive checkpoint ligand molecules like PD-L1 and CTLA-4, which can restrict T cell growth and function biologically, are often upregulated in tumor cells during immunotherapeutic treatment.245,433,491 ICBs are combined with neoantigen vaccines to prevent immune escape.245. This evidence concerns the gene CTLA4 and neoplasm.