These changes include upregulation of the inhibitory immune checkpoint receptors PD-1 and CTLA-4 [53,54] and downregulation of co-stimulatory molecules (e.g., CD28) on T cells, as well as reduction of the major histocompatibility complex (MHC) antigens class I, increase of the inhibitory ligand PD-L1 [53] and reduced presentation of tumor specific (TS), or tumor associated (TA) antigens on cancer cells [49,55]. Here, CD28 is linked to neoplasm.