Targeting GPC3^high cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in gastric cancer.

ABSTRACT: 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 GPC3^high CAFs have lower response rate to PD-1 therapy. GPC3 secreted from CAFs up-regulated PD-L1, TIM3

SUBMITTER: Li D 

PROVIDER: S-EPMC10088929 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature