CXCL12 and neoplasm: On the other hand, CAR-T cells have been inefficient in treating solid tumors such as melanoma due to multiple factors including tumor expression of programmed death ligand-1 (PD-L1: causing T-cell exhaustion), extracellular release of inhibitory cytokines (e.g., CXCL1, CXCL5, and CXCL12), hypoxic microenvironments, and distorted tumor vasculature, which impairs immune functions [159,166].