PDE5A and neoplasm: The main strategies to target MDSC and consequently their crosstalk with NK cells include: (i) regulation of myelopoiesis and MDSC depletion (tyrosine kinase inhibitors, cytotoxic agents), (ii) enhancement of MDSC differentiation (ATRA, Vitamin A, D3), (iii) inhibition of MDSC recruitment at the site of tumor (CCR5 antagonist, CCL2 inhibitor) (132, 162), (iv) inhibition of MDSC-mediated immunosuppression (STAT3 inhibitors, PDE5, histone deacetylase, NO inhibitors, Arginase inhibitors, ROS inhibitors, COX-2 inhibitors, phenformin, metformin, Polyinosinic-polycytidylic acid) (Figure 3).