Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, PR China; Heilongjiang Key Laboratory of Molecular Oncology, No. 150 Haping Road, Nangang District, Harbin 150081, PR China.
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China; Heilongjiang Key Laboratory of Molecular Oncology, No. 150 Haping Road, Nangang District, Harbin 150081, PR China.
Cell Immunol. 2021 Aug;366:104384. doi: 10.1016/j.cellimm.2021.104384. Epub 2021 May 23.
Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in colorectal cancer (CRC). Stimulator of interferon genes (STING) is a novel potential target and STING agonists have shown potential anti-tumor efficacy. Combined therapy based on synergistic mechanism can overcome the resistance. However, STING agonists-based combination therapies are deficient. We designed different immunotherapy combinations, including STING agonist, indoleamine 2,3 dioxygenase (IDO) inhibitor and PD-1 blockade, with purpose of exploring which option can effectively inhibit CRC growth. To further explore the possible reasons of therapeutic effectiveness, we observed the combination therapy in C57BL/6 mice. Our findings demonstrated that STING agonist diABZI combined with IDO inhibitor 1-MT significantly inhibited tumor growth, even better than the three-drug combination, promoted the recruitment of CD8 T cells and dendritic cells, and decreased the infiltration of myeloid-derived suppressor cells. We conclude that diABZI combined with 1-MT is a promising option for CRC.
尽管免疫检查点阻断的癌症免疫疗法取得了令人印象深刻的临床成功，但在结直肠癌（CRC）中仍然无效。干扰素基因刺激物（STING）是一种新的潜在靶点，STING 激动剂已显示出潜在的抗肿瘤疗效。基于协同机制的联合治疗可以克服耐药性。然而，基于 STING 激动剂的联合治疗方案还存在不足。我们设计了不同的免疫治疗组合，包括 STING 激动剂、吲哚胺 2,3 双加氧酶（IDO）抑制剂和 PD-1 阻断剂，目的是探索哪种方案能有效抑制 CRC 生长。为了进一步探讨治疗效果的可能原因，我们在 C57BL/6 小鼠中观察了联合治疗。我们的研究结果表明，STING 激动剂 diABZI 与 IDO 抑制剂 1-MT 联合使用可显著抑制肿瘤生长，甚至优于三药联合治疗，促进了 CD8 T 细胞和树突状细胞的募集，并减少了髓系来源抑制细胞的浸润。我们得出结论，diABZI 联合 1-MT 是 CRC 的一种有前途的治疗选择。
