卵巢癌
肿瘤微环境
免疫系统
癌症研究
细胞毒性T细胞
免疫疗法
生物
上睑下垂
免疫检查点
癌细胞
癌症
免疫学
炎症
体外
炎症体
生物化学
遗传学
作者
Shourong Wang,Yao Liu,Huimin Xiao,Zhongshao Chen,Xiaohang Yang,Jingjing Yin,Yingwei Li,Cunzhong Yuan,Yan Shi,Gang Chen,Qinglei Gao,Beihua Kong,Chaoyang Sun,Kun Song
标识
DOI:10.1038/s41419-023-06301-1
摘要
Abstract Ovarian cancer is resistant to immune checkpoint blockade (ICB) treatment. Combination of targeted therapy and immunotherapy is a promising strategy for ovarian cancer treatment benefit from an improved immune microenvironment. In this study, Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) cohorts were used to screen prognosis and cytotoxic lymphocyte infiltration-associated genes in upregulated genes of ovarian cancer, tissue microarrays were built for further verification. In vitro experiments and mouse (C57/BL6) ovarian tumor (ID8) models were built to evaluate the synergistic effect of the combination of SF3B1 inhibitor and PD-L1 antibody in the treatment of ovarian cancer. The results show that SF3B1 is shown to be overexpressed and related to low cytotoxic immune cell infiltration in ovarian cancer. Inhibition of SF3B1 induces pyroptosis in ovarian cancer cells and releases mitochondrial DNA (mtDNA), which is englobed by macrophages and subsequently activates them (polarization to M1). Moreover, pladienolide B increases cytotoxic immune cell infiltration in the ID8 mouse model as a SF3B1 inhibitor and increases the expression of PD-L1 which can enhance the antitumor effect of αPDL1 in ovarian cancer. The data suggests that inhibition of SF3B1 improves the immune microenvironment of ovarian cancer and synergizes ICB immunotherapy, which provides preclinical evidence for the combination of SF3B1 inhibitor and ICB to ovarian cancer treatment.
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