癌相关成纤维细胞
癌症
医学
Glypican 3型
癌症研究
免疫疗法
肿瘤微环境
成纤维细胞活化蛋白
生物标志物
癌细胞
靶向治疗
内科学
肿瘤科
生物
生物化学
作者
Dinuo Li,Yu Wang,Ce Shi,Shuai Fu,Yifei Sun,Chen Li
标识
DOI:10.1080/07853890.2023.2189295
摘要
Cancer-associated fibroblasts (CAFs) are an important part of tumour microenvironment, but its role in immunotherapy of gastric cancer (GC) is still needed to further study. In this study, we firstly distinguish the GC related CAFs via single cell sequencing dataset. CAFs in deep layers of GC tissues gain more developmental potential. Moreover, we found Glypican-3 (GPC3) is up-regulated in the CAFs subgroups of the advanced GC and correlated with poor prognosis in GC patients. In addition, higher GPC3 expression GC patients have higher TIDE (Tumour Immune Dysfunction and Exclusion) score, dysfunction and exclusion score. independent GC cohort also show GC patients with GPC3high CAFs have lower response rate to PD-1 therapy. GPC3 secreted from CAFs up-regulated PD-L1, TIM3, CD24, CYCLIN D1, cMYC and PDK mRNA expression level in HGC-27 cells. At last, in vivo model demonstrate that targeting GPC3high CAFs sensitizing the PD-1 blockage therapy in GC. In conclusion, GPC3 expression in CAFs is a critical prognostic biomarker, and targeting GPC3high cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in GC.Key messagesGlypican-3 (GPC3) is up-regulated in the CAFs subgroups of the advanced gastric cancer.Gastric cancer patients with GPC3high CAFs have lower response rate to PD-1 therapy.Targeting GPC3high CAFs sensitizing the PD-1 blockage therapy in gastric cancer.
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