Apart from checkpoint mediators such as PD-1 and CTLA-4 a number of cell types have been identified that contribute to immune tolerance and evasion in the TME, Myeloid-derived suppressor cells (MDSCs), T regs, tumor associated macrophages (TAMs) and cancer associated fibroblasts all contribute to this immune suppression (246). This evidence concerns the gene CTLA4 and neoplasm.