ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1637300
Extracellular Matrix Remodeling Fibroblasts Govern the Tumor Microenvironment Disparity between Adenomatous Lesions and Adenocarcinoma in Gallbladder
Provisionally accepted
- 1Shengjing Hospital of China Medical University Department of General Surgery, Shenyang, China
- 2Sheng Jing Hospital Affiliated, China Medical University, Shenyang, China
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The adenoma-carcinoma sequence is a widely recognized yet poorly described model for gallbladder oncogenesis. In our study, single-cell RNA sequencing was performed on cells from four gallbladder cancer (GBC) and four gallbladder adenomatous lesions (GBA) samples.The results revealed that the epithelial-mesenchymal transition plays a key role in mediating the malignant transformation of epithelial cells from GBA to GBC. Compared to GBA, the immune landscape of GBC is predominantly immunosuppressive. In GBC, macrophages with high chemotaxis ability and an M2 phenotype are prevalent, while GBA typically has M1 phenotype macrophages. GBC also shows enrichment of tumor-promoting LAMP3 + dendritic cells (DCs) and plasmacytoid DCs, whereas inflammatory monocyte-derived DCs preferentially accumulate in the GBA microenvironment. Moreover, GBC is marked by increased immunosuppressive regulatory T cells and exhausted T cells, while GBA contains more immature cytotoxic T cells. We also identified a subset of fibroblasts with extracellular matrix remodeling capabilities. These fibroblasts drive the differences in the tumor microenvironment (TME) between GBC and GBA through COL1A2-mediated cell communication. This work elucidates the distinct roles of various cell types in the TME of GBA and GBC and emphasizes the need to understand the mechanisms of malignant transformation from adenomatous lesions to carcinoma in the gallbladder.
Keywords: Tumor Microenvironment, Cancer-associated fibroblast, gallbladder cancer, gallbladder adenomatous lesions, Collagen
Received: 29 May 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Ma, Huixin, Rongli, Lv and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chao Lv, Shengjing Hospital of China Medical University Department of General Surgery, Shenyang, China
Yu Tian, Sheng Jing Hospital Affiliated, China Medical University, Shenyang, China
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