IDO inhibitor synergized with radiotherapy to delay tumor growth by reversing T cell exhaustion

作者：Meng Liu, Ziyang Li, Weirong Yao, Xiaoping Zeng, Lingyun Wang, Jiao Cheng, Bingyu Ma, Ruiqian Zhang, Wei‐Ping Min, Hongmei Wang · 发表于：Molecular Medicine Reports · 年份：2019 · DOI：10.3892/mmr.2019.10816 · 被引用次数：41 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer, Stress, Anesthesia, and Immune Response、Tryptophan and brain disorders

Previous studies suggest that radiotherapy (RT) can induce immune activation, which not only reduces the progression of tumors, but also causes the release of tumor antigens. The combination of RT and immune checkpoint blockade, such as the inhibition of programmed cell death 1 (PD‑1) and programmed cell death ligand 1 (PD‑L1), has been demonstrated to yield impressive response rates. However, a substantial proportion of patients develop resistance such therapies. Previous studies have shown that indoleamine 2,3‑dioxygenase (IDO) causes T cell exhaustion and increased formation of regulatory T cells (Tregs), upregulating the expression of inhibitory receptors and ligands. Therefore, the application of IDO inhibitors combined with RT may have a synergistic effect by relieving immunosuppression. Lewis lung cancer cell‑bearing mice were treated with the IDO inhibitor 1‑methyl‑tryptophan (1MT) and/or 10 Gy RT. Tumor size was measured every day, flow cytometry was performed to measure the expression of dendritic cell (DC) maturation markers, inhibitory receptors, ligands, cytotoxic T cells and Treg phenotypic markers. Reverse transcription‑quantitative PCR was used to evaluate the mRNA expression levels of IDO, PD‑L1, PD‑1, T cell immunoglobulin domain and mucin domain 3 (TIM‑3), B‑ and T‑lymphocyte attenuator (BTLA) and galectin‑9. Compared with the control group, treatment with 1MT or RT reduced tumor growth, however, the combination therapy was more effective than either treatm...