Çakal S, Er Urgancı B, Şimşek S. Key players in the breast cancer microenvironment: From fibroblasts to immune cells. World J Clin Oncol 2025; 16(7): 107339 [DOI: 10.5306/wjco.v16.i7.107339]
Corresponding Author of This Article
Sacide Çakal, MSc, Department of Medical Biology, Pamukkale University, Faculty of Medicine, Morphology Building, Floor:3, Denizli, 20070 Türkiye. scakal21@posta.pau.edu.tr
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Jul 24, 2025; 16(7): 107339 Published online Jul 24, 2025. doi: 10.5306/wjco.v16.i7.107339
Key players in the breast cancer microenvironment: From fibroblasts to immune cells
Sacide Çakal, Buket Er Urgancı, Selda Şimşek
Sacide Çakal, Buket Er Urgancı, Selda Şimşek, Department of Medical Biology, Pamukkale University, Faculty of Medicine, Denizli 20070, Türkiye
Author contributions: Çakal S performed the majority of the writing; Urgancı BE and Şimşek S prepared and designed the outline and coordinated the writing of the paper.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sacide Çakal, MSc, Department of Medical Biology, Pamukkale University, Faculty of Medicine, Morphology Building, Floor:3, Denizli, 20070 Türkiye. scakal21@posta.pau.edu.tr
Received: April 1, 2025 Revised: April 21, 2025 Accepted: June 3, 2025 Published online: July 24, 2025 Processing time: 115 Days and 20.2 Hours
Abstract
Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women. Beyond tumor cells, the tumor microenvironment (TME) also plays an important role in cancer progression, therapy resistance, and metastasis. The TME is a complex ecosystem consisting of stromal and immune cells, extracellular matrix (ECM), and various signaling molecules that dynamically interact with tumor cells. Cancer-associated fibroblasts remodel the ECM and secrete growth factors that promote tumor growth and invasion. Immune cells, such as tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, often contribute to an immunosuppressive environment that hinders anti-tumor immune responses. The ECM provides structural support and acts as a reservoir for signaling molecules that influence cancer cell behavior. These components evolve together with tumor cells, facilitating immune evasion, therapy resistance, and epithelial-to-mesenchymal transition, which promotes metastasis. Understanding these interactions is necessary to develop novel therapeutic strategies that target both tumor and microenvironmental components. This minireview highlights the key stromal and immune elements within the breast cancer microenvironment, discussing their individual and collective roles in tumor progression and clinical outcomes, while emphasizing emerging therapeutic approaches aiming to reprogram the TME to improve treatment efficacy.
Core Tip: The tumor microenvironment (TME) in breast cancer is a complex and dynamic ecosystem consisting of immune cells, stromal components, and the extracellular matrix. This review investigates how key players in the TME, including cancer-associated fibroblasts, tumor-infiltrating lymphocytes, and macrophages, contribute to tumor progression, immune modulation, and metastasis. Understanding these interactions sheds light on the mechanisms driving breast cancer heterogeneity and disease progression.
