[摘 要] 目的：探讨吲哚胺2,3-双加氧酶（IDO）抑制剂1-左旋-甲基色氨酸（1-L-MT）对树突状细胞（DC）功能的影响，评估其 与DC疫苗联合治疗结直肠癌小鼠移植瘤的效果及免疫机制。方法：采用WB法检测DC中IDO的表达水平；1-L-MT处理DC 后，流式细胞术分析DC表面标志物（CD11c、CD40、CD80、CD86）的表达变化。将1-L-MT处理的抗原致敏DC与T细胞共培养， 通过检测DC诱导产生的T细胞，评估1-L-MT对DC诱导特异性T细胞增殖能力及其对CD8? T细胞比例的影响。体外细胞毒性 实验检测1-L-MT处理下DC诱导的特异性T细胞对结直肠癌细胞CT26的杀伤作用；建立CT26细胞荷瘤小鼠模型，评估1-L-MT 与DC疫苗联用的安全性、抑瘤效果及生存获益。结果：DC在分化后期IDO蛋白表达上调，经1-L-MT处理后其成熟标志物 CD40表达显著上调（P < 0.05），所诱导的抗原特异性T细胞的增殖能力（P < 0.01）、CD8? T细胞的比例（P < 0.05）、对CT26细胞 的特异性杀伤能力（P < 0.01）均显著增强。体内实验表明，1-L-MT与DC疫苗联用未观察到明显毒性，并能显著抑制肿瘤 生长（P < 0.01），延长荷瘤小鼠生存期（P < 0.05）。结论：1-L-MT可通过上调CD40表达促进DC成熟及增强其T细胞活化功能， 与DC疫苗联用显著提升抗原特异性T细胞应答，抑制结直肠癌移植瘤进展、延长荷瘤小鼠生存期。

[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.

[基金项目] 国家自然科学基金（No. 81671644）