Thus, in the CRC TME, three factors synergize to form an extensive immunosuppressive network: Trp depletion driven by excessive IDO1/TDO2 activity, massive kynurenine (Kyn) accumulation, and elevated 5-HT levels resulting from Trp shunting into 5-HT synthesis. The gene discussed is IDO1; the disease is colorectal carcinoma.