Synergistically, tumor cells and immunosuppressive cells [e.g., Regulatory T cells (Tregs), Tumor-associated macrophages (TAMs), Myeloid-derived suppressor cells (MDSCs), and Cancer-associated fibroblasts (CAFs)] produce inhibitory mediators like Prostaglandin E2 (PGE2), IDO, CTLA4, PD-L1, IL-10, and TGF-β as well as activate the negative signals that result in immunosuppressive TME. The gene discussed is IDO1; the disease is neoplasm.