PDCD1 and colorectal carcinoma: Moreover, a mechanism involving the VEGF-A-induced expression of the transcription factor TOX, a well-known marker of CD8+ T cell exhaustion [39], in TILs of CRC has been identified as one of the main causes of the resistance to anti PD-1 therapy, suggesting that reduction of VEGF-A levels in tumor tissue might also impact on T cell exhaustion [40].