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doi: 10.1016/j.cmet.2014.10.006 61 FalonyGVieira-SilvaSRaesJ

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In our recent preclinical studies, dual inhibition of IDO1 and TDO2 with the novel agent AT-0174 effectively reduced KYN levels, increased tumor infiltration with natural killer cells, and reduced regulatory T cells in cisplatin-resistant lung cancer models ( These mechanisms were further substantiated in an aggressive model of glioblastoma where AT-0174 monotherapy increased natural killer cell infiltration, reduced Treg cells in tumor tissues, and was synergistic with Temozolomide (TMZ), an alkylating agent, in significantly prolonging animal survival ( In another study of high-grade serous carcinoma (HGSC), which is known to exhibit poor outcomes due to therapy resistance and an immunosuppressive TME, Crump et al