Revisiting the role of cancer-associated fibroblasts in tumor microenvironment DOI Creative Commons

Xiaolei Lan,

Wenyang Li, Kai Zhao

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 17, 2025

Cancer-associated fibroblasts (CAFs) are integral components of the tumor microenvironment playing key roles in progression, metastasis, and therapeutic resistance. However, challenges persist understanding their heterogeneity, origin, functional diversity. One major obstacle is lack standardized naming conventions for CAF subpopulations, with current systems failing to capture full complexity. Additionally, identification CAFs hindered by absence specific biomarkers, limiting precision diagnostic strategies. In vitro culture conditions often fail maintain vivo characteristics CAFs, which complicates study translation findings clinical practice. Although detection methods, such as antibodies, mRNA probes, single-cell transcriptomics, offer insights into biology, they standardization provide reliable quantitative measures. Furthermore, dynamic interactions between cells, immune cells within TME remain insufficiently understood, role evasion therapy resistance an area ongoing research. Understanding how influence drug response essential developing more effective cancer therapies. This review aims in-depth analysis research, propose future research directions, emphasize need improved CAF-targeted By addressing these gaps, it seeks highlight potential targets overcoming enhancing efficacy treatments.

Язык: Английский

Antigen-presenting cancer-associated fibroblasts in murine pancreatic tumors differentially control regulatory T cell phenotype and function via CXCL9 and CCL22 DOI Creative Commons
Saumya Maru,

M. Wetzel,

Jacob T. Mitchell

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a complex tumor microenvironment (TME) including stromal cells that influence resistance to therapy. Recent studies have revealed cancer-associated fibroblasts (CAFs) are heterogeneous in origin, gene expression, and function. Antigen-presenting CAFs (apCAFs), defined major histocompatibility (MHC)-II expression can activate effector CD4 + T the potential contribute anti-cancer immune response, but also induce regulatory cell (Treg) differentiation. Whether apCAFs promote or restrain antitumor response remains uncertain. Using clones of KPC murine PDAC model differing sensitivity checkpoint blockade (ICB), we found immunosensitive (sKPC) tumors were higher apCAF infiltration than resistant (rKPC) tumors. IMC analysis showed proximity both sKPC rKPC implicating interaction within TME. apCAF-depleted tumor-bearing mice had diminished ICB. from activated tumor-infiltrating induced Treg However, transcriptomic Tregs overexpressed for immunosuppressive genes rKPCs relative sKPCs, this associated with differential chemokine signaling depending on origin. Together these data implicate as important mediators modulation which could facilitate development more effective anti-tumor based approaches patients.

Язык: Английский

Процитировано

0
Revisiting the role of cancer-associated fibroblasts in tumor microenvironment DOI Creative Commons

Xiaolei Lan,

Wenyang Li, Kai Zhao

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 17, 2025

Cancer-associated fibroblasts (CAFs) are integral components of the tumor microenvironment playing key roles in progression, metastasis, and therapeutic resistance. However, challenges persist understanding their heterogeneity, origin, functional diversity. One major obstacle is lack standardized naming conventions for CAF subpopulations, with current systems failing to capture full complexity. Additionally, identification CAFs hindered by absence specific biomarkers, limiting precision diagnostic strategies. In vitro culture conditions often fail maintain vivo characteristics CAFs, which complicates study translation findings clinical practice. Although detection methods, such as antibodies, mRNA probes, single-cell transcriptomics, offer insights into biology, they standardization provide reliable quantitative measures. Furthermore, dynamic interactions between cells, immune cells within TME remain insufficiently understood, role evasion therapy resistance an area ongoing research. Understanding how influence drug response essential developing more effective cancer therapies. This review aims in-depth analysis research, propose future research directions, emphasize need improved CAF-targeted By addressing these gaps, it seeks highlight potential targets overcoming enhancing efficacy treatments.

Язык: Английский

Процитировано

0