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Archive > Volume 32 Issue 11 > 2025,32(11):1115-1120. DOI:10.3872/j.issn.1007-385X.2025.11.002 Prev Next
Basic Research
IDO inhibitor 1-L-MT enhances the efficacy of dendritic cell vaccines against colorectal cancer
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Abstract:
[Abstract] Objective: To investigate the impact of indoleamine 2,3-dioxygenase (IDO) inhibitor 1-L-methyltryptophan (1-L-MT) on dendritic cell (DC) function and the therapeutic efficacy of combining IDO inhibition with DC vaccination against colorectal cancer. Methods: IDO expression in DCs was determined by WB assay. After treatment with 1-L-MT, phenotypic changes in DC surface markers were analysed by flow cytometry. Antigen-pulsed DCs pretreated with 1-L-MT were co-cultured with T cells. The subsequent T cell response was analyzed to evaluate the effect of 1-L-MT on the capacity of DCs to induce antigen-specific T cell proliferation and to modulate the CD8? T cell proportion. In vitro cytotoxicity assays evaluated the tumoricidal activity of 1-L-MT–modulated DC-induced antigen-specific T cells against the colorectal cancer cell line CT26. A murine tumor-bearing model was established to assess the safety and antitumor efficacy of combined 1-L-MT and DC vaccination. Results: DCs constitutively expressed IDO protein. Following 1-L-MT treatment, the maturation marker CD40 was significantly up-regulated (P < 0.05). DCs exposed to 1-L-MT exhibited enhanced capacity to promote antigen-specific T-cell proliferation (P < 0.01), increased CD8? T-cell proportion (P < 0.05), and potentiated specific lysis of CT26 tumor cells (P < 0.01). In vivo, combined 1-L-MT and DC vaccine markedly suppressed tumor growth (P < 0.01) and prolonged survival (P < 0.05). Conclusion: 1-L-MT promotes DC maturation and enhances their immune-activating function by boosting T cell activation. Combined with DC vaccination, it significantly amplifies antigen-specific T-cell responses, restrains colorectal cancer progression, and extends survival, indicating promising clinical translational potential.
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