Volume 49, Issue 3 (12-2025)
Research in Medicine 2025, 49(3): 47-69 |
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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) :47-69
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: (259 Views)
Background and Aim: Although standard chemotherapy based on the maximum tolerated dose (MTD) exerts cytotoxic effects, it may also cause immunosuppression. In contrast, metronomic chemotherapy (mCHT), administered as continuous or frequent low doses, has anti- angiogenic effects and has been proposed as an immunomodulatory strategy. This systematic review aimed to summarize the evidence on the effects of mCHT on immune responses- both systemic and within the tumor microenvironment- in breast cancer, and to evaluate the related clinical and translational outcomes.
Methods: A systematic search was conducted in PubMed / MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library for studies published from January 2000 to the date of the study. Preclinical and clinical breast cancer studies evaluating mCHT and reporting immune parameters (such as tumor- infiltrating lymphocytes [TILs], regulatory T cells [Treg], myeloid- derived suppressor cells [MDSCs], dendritic cells [DCs], and cytokines) and / or clinical outcomes were included. Study selection, data extraction, and risk of bias assessment were performed independently by two reviewers using the RoB 2, ROBINS-I, and SYRCLE tools.
Results and Conclusion: In most studies, mCHT was associated with a reduction in immunosuppressive cell populations (particularly Treg and MDSCs), enhanced T-cell and NK-cell function, and favorable changes in the tumor microenvironment, including increased lymphocyte infiltration. However, heterogeneity in treatment regimens and endpoints limited quantitative synthesis. These findings suggest that metronomic chemotherapy has significant potential for immune priming and may enhance combination therapeutic strategies, including immunotherapy, in breast cancer. To define its precise clinical role, standardization of immune metrics and 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 for studies published from January 2000 to the date of the study. Preclinical and clinical breast cancer studies evaluating mCHT and reporting immune parameters (such as tumor- infiltrating lymphocytes [TILs], regulatory T cells [Treg], myeloid- derived suppressor cells [MDSCs], dendritic cells [DCs], and cytokines) and / or clinical outcomes were included. Study selection, data extraction, and risk of bias assessment were performed independently by two reviewers using the RoB 2, ROBINS-I, and SYRCLE tools.
Results and Conclusion: In most studies, mCHT was associated with a reduction in immunosuppressive cell populations (particularly Treg and MDSCs), enhanced T-cell and NK-cell function, and favorable changes in the tumor microenvironment, including increased lymphocyte infiltration. However, heterogeneity in treatment regimens and endpoints limited quantitative synthesis. These findings suggest that metronomic chemotherapy has significant potential for immune priming and may enhance combination therapeutic strategies, including immunotherapy, in breast cancer. To define its precise clinical role, standardization of immune metrics and 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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