PDCD1 and cancer: Immunosuppressive cytokines VEGF produced by Treg cells will inhibit the activation and development of CTL directly or inhibit APC mature and CTL priming indirectly.184,185 Tumour neovascularization further aggravates the hypoxic and low PH environment, which in turn reduces the infiltration of effective T cells.186 Other stromal cells, for instance, cancer-associated fibroblasts (CAFs) contribute to anti-PD-1 or anti-PD-L1 resistance.187