Zheng Xichen, Kuai Jiajie, Shen Guanghui
Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, 200000, China.
Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory & Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory & Immune Medicine, Anhui Medical University, Hefei, 230000, China.
Immunotherapy. 2023 Apr;15(6):429-442. doi: 10.2217/imt-2022-0254. Epub 2023 Mar 7.
Immunotherapy has revolutionized cancer management. However, response to immunotherapy is heterogeneous. Thus, strategies to improve antitumor immune responses in resistant tumors, such as breast cancer, are urgently needed. Established murine tumors were treated with anti-CTLA4 or anti-PD-1 alone or combined with metronomic gemcitabine (met-GEM). Tumor vascular function, immune cell tumor infiltration and gene transcription were determined. Low-dose met-GEM (2 mg/kg) treatments improved tumor vessel perfusion and increased tumor-infiltrating T cells. Notably, low-dose met-GEM pretreatments converted resistant tumors to respond to immunotherapy. Moreover, combined therapy reduced tumor vessel density, improved tumor vessel perfusion, increased T-cell tumor infiltration and upregulated the expression of some anticancer genes. Low-dose met-GEM pretreatment reconditioned the tumor immune microenvironment and improved immunotherapy efficacy in murine breast cancer.
免疫疗法彻底改变了癌症治疗方式。然而，对免疫疗法的反应存在异质性。因此，迫切需要采取策略来改善耐药性肿瘤（如乳腺癌）中的抗肿瘤免疫反应。对已建立的小鼠肿瘤单独使用抗CTLA4或抗PD-1进行治疗，或与节拍性吉西他滨（met-GEM）联合使用。测定肿瘤血管功能、免疫细胞肿瘤浸润和基因转录情况。低剂量met-GEM（2mg/kg）治疗可改善肿瘤血管灌注并增加肿瘤浸润性T细胞。值得注意的是，低剂量met-GEM预处理可使耐药性肿瘤对免疫疗法产生反应。此外，联合治疗降低了肿瘤血管密度，改善了肿瘤血管灌注，增加了T细胞肿瘤浸润，并上调了一些抗癌基因的表达。低剂量met-GEM预处理重塑了肿瘤免疫微环境，并提高了小鼠乳腺癌免疫疗法的疗效。
