Overexpression of cyclooxygenase (COX)-2 in tumor cells leads tointratumoral production of the immunosuppressive bioactive lipid metabolitePGE2, which not only promotes accumulation of MDSCs and M2-like TAMspolarization but also restricts tumor infiltration and cytokine (e.g.,IL-2 and IFN-γ) secretion in Teff cells.147,148 Inhibition of COX has been incorporated into clinical trials toassess its impact on the effectiveness of ICIs-based tumor immunotherapies(NCT03638297, NCT02659384, and NCT03245489; Table 1). The gene discussed is IFNG; the disease is neoplasm.