Volume 49, Issue 3 (12-2025)
Research in Medicine 2025, 49(3): 0-0 |
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Ghorbani Vanan A, Abedian A, Shabani M. A review of the effects of metronomic chemotherapy on the immune system and the tumor microenvironment in breast cancer: preclinical and clinical studies. Research in Medicine 2025; 49 (3)
URL: http://pejouhesh.sbmu.ac.ir/article-1-3511-en.html
URL: http://pejouhesh.sbmu.ac.ir/article-1-3511-en.html
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran , msshabani@sbmu.ac.ir
Abstract: (5 Views)
Background and Objectives: Although standard chemotherapy based on the maximum tolerated dose (MTD) exerts cytotoxic effects, it may also be associated with immunosuppression. In contrast, metronomic chemotherapy (mCHT), administered as continuous or frequent low doses, in addition to its anti-angiogenic effects, has been proposed as an immunomodulatory strategy. The aim of this systematic review was to summarize the evidence on the effects of mCHT on immune responses (systemic and within the tumor microenvironment) in breast cancer and the related clinical/translational outcomes.
Methods: A systematic search was conducted in PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library from January 2000 until the date of the study. Preclinical and clinical breast cancer studies evaluating mCHT and reporting immune parameters (such as TILs, Treg, MDSC, DCs, cytokines) and/or clinical outcomes were included. Study selection, data extraction, and risk of bias assessment were performed independently by two reviewers using RoB 2, ROBINS-I, and SYRCLE tools.
Results and Conclusion: In most studies, mCHT was associated with a relative reduction in immunosuppressive cell populations (particularly Treg and MDSC), improved T-cell and NK-cell function, and favorable changes in the tumor microenvironment, including enhanced lymphocyte infiltration. However, heterogeneity in treatment regimens and endpoints limited quantitative synthesis. Thus, metronomic chemotherapy has significant potential for immune priming and for enhancing combination therapeutic strategies, including immunotherapy, in breast cancer. Nevertheless, to define its precise clinical role, standardization of immune metrics and the conduct of comparative trials incorporating predictive biomarkers are essential.
Methods: A systematic search was conducted in PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library from January 2000 until the date of the study. Preclinical and clinical breast cancer studies evaluating mCHT and reporting immune parameters (such as TILs, Treg, MDSC, DCs, cytokines) and/or clinical outcomes were included. Study selection, data extraction, and risk of bias assessment were performed independently by two reviewers using RoB 2, ROBINS-I, and SYRCLE tools.
Results and Conclusion: In most studies, mCHT was associated with a relative reduction in immunosuppressive cell populations (particularly Treg and MDSC), improved T-cell and NK-cell function, and favorable changes in the tumor microenvironment, including enhanced lymphocyte infiltration. However, heterogeneity in treatment regimens and endpoints limited quantitative synthesis. Thus, metronomic chemotherapy has significant potential for immune priming and for enhancing combination therapeutic strategies, including immunotherapy, in breast cancer. Nevertheless, to define its precise clinical role, standardization of immune metrics and the conduct of comparative trials incorporating predictive biomarkers are essential.
Keywords: Breast cancer, metronomic chemotherapy, MTD, MDSCs, tumor microenvironment, TILs, Treg, immunomodulation.
Type of Study: Review |
Subject:
Immunology
Received: 2025/12/16 | Accepted: 2026/01/6 | Published: 2026/02/16
Received: 2025/12/16 | Accepted: 2026/01/6 | Published: 2026/02/16
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