PD-1 is a marker of T cell exhaustion and plays a critical role in restraining tumour rejection by CD8+ T cells, which are endowed with the potential to recognize tumour antigens and to directly kill transformed cells trough the release of granules containing cytotoxic substances such as perforin, granzymes, tumour necrosis factor alpha (TNF-α) and membrane-anchored Fas-ligand [30]. Here, TNF is linked to neoplasm.