IDO抑制剂NLG919联合伊立替康抗小鼠结肠癌CT26研究

Antitumor Effects of Combination IDO Inhibitor NLG919 with Irinotecan in CT26-bearing Mice

本文旨在研究吲哚胺-2,3双加氧酶(IDO)抑制剂NLG919及联合化疗药伊立替康的抗肿瘤作用以及潜在的作用机制.实验以IDO抑制剂NLG919为基础,采用小鼠结肠癌CT26荷瘤小鼠模型,研究了NLG919与化疗药物伊立替康联用的抗肿瘤作用及免疫机制.研究结果表明,NLG919与伊立替康联用时未增加其动物体重降低作用; NLG919可显著增强伊立替康的抗肿瘤作用,其机制与改善肿瘤免疫微环境有关,包括提高CD3+CD4+、CD3+CD8+效应T细胞比例和增强细胞因子γ-干扰素和白细胞介素-2的分泌.基于IDO抑制剂的免疫治疗与化疗药物联用可作为一种提高抗肿瘤效应的重要策略.

The aim of this study is to investigate the antitumor effects and mechanisms of indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919 combined with irinotecan in CT26-bearing mice. NLG919 in combination with irinotecan shows synergistic antitumor effects by increasing the percentages of CD3^+CD4^+and CD3^+CD8^+T cells, and by enhancing the secretions of interferon-γ and interleukin-2. These findings indicate that NLG919 can potentiate the antitumor efficacy of irinotecan without increasing its side effects in body weight. It also suggests that the combination of IDO inhibitor-based immunotherapy with chemotherapy might serve as a new potential strategy for cancer treatment.