Editorial: Role of Fibroblast in Cancer

Xuezhen Zeng ^1* MAN LIU ²

• ¹ Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
• ² Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

emerged as a promising strategy for cancer therapy 6 . This Research Topic brings together cutting-edge research and review on the pivotal role of fibroblast in cancer and therapeutic potential.In this section, Cheng et al. 7 analyzed 5190 publications related to CAFs by bibliometric tools such as VOSviewer and CiteSpace. They found that China and the United States were the leading contributors in terms of publications, funding agencies, and international collaborations. Among all the CAF-associated studies, breast, colorectal, pancreatic, prostate and gastric cancer were the top 5 studied cancers. And CAFs have been demonstrated to correlate with immune cell infiltration (including T cells, B cells, tumor-associated macrophages), antitumor immunity or immunosuppression, the efficacy of immunotherapy (PD-L1), cancer cell stemness, and DNA methylation, etc. Several genes such as TGFB1, IL-6, TNF, TP53, and VEGFA, and pathways such as HIF-1 and Toll-like receptor signaling have been highlighted in these studies. This article provides a overview of the CAF-related studies, highlighting current trends and future directions with a focus on advancements in the tumor immune microenvironment.Immunotherapy has revolutionized the treatment of cancers, with its effectiveness significantly influenced by the tumor microenvironment.Cancer-associated fibroblasts (CAFs) have emerged as promising targets to enhance the efficacy of immunotherapy, but specific CAF marker is lacking.Xia et al. 8 has developed a CAF Angiogenesis Prognostic Score (CAPS) system in gastric cancer (GC) patients. Several differentially expressed genes associated with CAF-angiogenesis were identified, including THBS1, SPARC, EDNRA, and VCAN, which were used to establish the CAPS. RT-qPCR experiment, GEO datasets, and the HPA database were utilized to validate the CAPS gene expression. In addition, high-CAPS correlated with shorter overall survival and a tendency toward immune escape and reduced immunotherapy efficacy. Thus, CAPS serves as an independent predictor of GC prognosis and immunotherapy efficacy.In prostate cancer (PCa), Torres et al. 9 unraveled that PCa associated fibroblasts (PCAFs) displayed different metabolic and functional profile compared to normal prostate fibroblasts (PFs). PCAFs exhibited reduced ECM degradation activity under normoxic condition compared to PFs. In addition, PCAFs and PFs displayed distinct metabolic characteristics under both normoxic and hypoxic conditions. Moreover, PCAFs expressed higher level of PD-L1 under hypoxia, which was not observed in PFs. These results suggest that PCAFs may foster an immunosuppressive tumor microenvironment, particularly under hypoxic conditions. Fibroblast Growth Factor Receptors (FGFRs) are a family of receptor tyrosine kinases that are widely expressed on cell surfaces and play essential roles in both embryonic development and adult tissue homeostasis. Accumulating evidence indicates that FGFR-driven oncogenesis is frequently associated with gene amplification, activating mutations, or chromosomal translocations across a wide range of tumor types. Aberrant FGFR signaling has been linked to numerous malignancies, including bladder, stomach, and lung cancers.Given their pivotal role, FGFRs represent attractive targets for anticancer therapies. Popiel et al. 10 reported that CPL304100, a novel and potent inhibitor targeting FGFR1-3 kinase domains exhibited robust biological activity in vitro. Gastrointestinal (GI) cancers, including colorectal, gastric, liver, oesophageal, and pancreatic cancer, are a major cause of morbidity and mortality worldwide.Gastric cancer is one of the most aggressive malignancies, which is resistant to various cancer treatments. Accmulating studies identify CAFs as the leading factor contributing to an unfavorable tumor immune microenvironment and poor prognosis in gastric cancer patients. Ozmen et al. 12