biostudies-literatureUnknownShen ZQGovernment of Jiangsu ProvinceNational Natural Science Foundation of ChinaImmunotherapy targeting immune checkpoints has emerged as a promising strategy in cancer treatment; however, the heterogeneous and dynamic tumor microenvironment (TME) imposes critical constraints on therapeutic outcomes. Tryptophan 2,3-dioxygenase (TDO), often dysregulated in malignant tissues, plays a pivotal role in shaping an immunosuppressive milieu by depleting tryptophan, thereby hindering anti-tumor immune response. To counteract this immune evasion mechanism, we designed a novel indole-coordinated ruthenium(ii) arene complex (In-Ru), aimed at bolstering tumor immunotherapy and thwarting immune evasion by targeting TDO expression. Our findings reveal that In-Ru exerts markedly potent anti-proliferative effects against HepG2 cells. It achieves this by specifically localizing to the Chemical sciencehttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12308519biostudies-literatureNovel tryptophan 2,3-dioxygenase-targeted ruthenium(ii)-indole complex activates immunotherapy <i>in vitro</i> and <i>in vivo</i>.PMC123085192247706222350001KYCX24-180522077066Liu HWang PShen ZQZhang YLiu HKRen MSu ZGuo BXue XDai XXu YfalseNovel tryptophan 2,3-dioxygenase-targeted ruthenium(ii)-indole complex activates immunotherapy <i>in vitro</i> and <i>in vivo</i>.Immunotherapy targeting immune checkpoints has emerged as a promising strategy in cancer treatment; however, the heterogeneous and dynamic tumor microenvironment (TME) imposes critical constraints on therapeutic outcomes. Tryptophan 2,3-dioxygenase (TDO), often dysregulated in malignant tissues, plays a pivotal role in shaping an immunosuppressive milieu by depleting tryptophan, thereby hindering anti-tumor immune response. To counteract this immune evasion mechanism, we designed a novel indole-coordinated ruthenium(ii) arene complex (In-Ru), aimed at bolstering tumor immunotherapy and thwarting immune evasion by targeting TDO expression. Our findings reveal that In-Ru exerts markedly potent anti-proliferative effects against HepG2 cells. It achieves this by specifically localizing to the 2025-01-01T00:00:00Z2025 Jul2026-05-28T02:17:14.77Z2025-08-27T03:06:51.249ZS-EPMC123085194074731810.1039/d5sc03778f