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• W4386385334 endingPage "107406" @default.
• W4386385334 startingPage "107406" @default.
• W4386385334 abstract "In the era of immunotherapy, the suboptimal response rate and the development of acquired resistance among the initial beneficiaries continue to present significant challenges across multiple malignancies, including gastric cancer (GC). Considering that the interactions of tumor stroma, especially the cancer-associated fibroblasts (CAFs), with immune and tumor cells, play indispensable roles in tumor progression, tumor microenvironment remodeling and therapeutic responsiveness, in-depth exploration on the roles of CAFs and pivotal mediators of their functions may provide novel clues to increase the effectiveness of current immunotherapeutic drugs and further achieve synergistic antitumor response. Herein, through the consensus clustering of canonical biomarkers, three GC subclasses with different abundance of CAFs were virtually microdissected in four integrated bulk cohorts encompassing 2148 GC patients from 11 independent datasets. An extensive immunogenomic analysis revealed that tumors with high CAFs infiltration were characterized with unfavorable outcomes, aggressive phenotypes, decreased tumor immunogenicity, high risk of immune evasion and thus immunotherapeutic resistance. By leveraging large-scale single-cell transcriptomic profiling, a series of CAF-secreted proteins were identified, among which the SERPINE2 was confirmed to be restrictively enriched in stromal fibroblasts of GC tissues and contribute to promoting a protumor milieu and fostering an immunosuppressive microenvironment via bioinformatics computations and tissue microarray analysis. Moreover, pan-cancer investigations generalized the immunological roles of SERPINE2, especially in pan-gastrointestinal malignancies, with multiple real-world immunotherapy cohorts further confirming its implications on predicting immunotherapeutic efficacy. In conclusion, these findings suggest the CAF-derived SERPINE2 is a promising immune-oncology target with therapeutic implications to further synergize the immunotherapeutic combinations." @default.
• W4386385334 created "2023-09-02" @default.
• W4386385334 creator A5005002539 @default.
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• W4386385334 creator A5028918974 @default.
• W4386385334 creator A5033875313 @default.
• W4386385334 creator A5045805155 @default.
• W4386385334 creator A5084047711 @default.
• W4386385334 date "2023-11-01" @default.
• W4386385334 modified "2023-10-03" @default.
• W4386385334 title "Microdissection of cancer-associated fibroblast infiltration subtypes unveils the secreted SERPINE2 contributing to immunosuppressive microenvironment and immuotherapeutic resistance in gastric cancer: A large-scale study integrating bulk and single-cell transcriptome profiling" @default.
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