Document detail
ID
oai:pubmedcentral.nih.gov:1008...
Topic
OncologyAuthor
Li, Dinuo Wang, Yu Shi, Ce Fu, Shuai Sun, Yi-Fei Li, ChenLangue
enEditor
Taylor & Francis
Category
Annals of Medicine
Year
2023
listing date
10/19/2023
Keywords
gc blockage sensitizing expression up-regulated cancer gastric targeting gpc3 therapy pd-1 cafsAbstract
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, CD24, CYCLIN D1, cMYC and PDK mRNA expression level in HGC-27 cells.
At last, in vivo model demonstrate that targeting GPC3(high) CAFs sensitizing the PD-1 blockage therapy in GC.
In conclusion, GPC3 expression in CAFs is a critical prognostic biomarker, and targeting GPC3(high) KEY MESSAGES: 1.
Glypican-3 (GPC3) is up-regulated in the CAFs subgroups of the advanced gastric cancer.
2.
Gastric cancer patients with GPC3(high) CAFs have lower response rate to PD-1 therapy.
3.
Targeting GPC3(high) CAFs sensitizing the PD-1 blockage therapy in gastric cancer.
Li, Dinuo,Wang, Yu,Shi, Ce,Fu, Shuai,Sun, Yi-Fei,Li, Chen, 2023, Targeting GPC3(high) cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in gastric cancer, Taylor & Francis
