Defining and targeting macrophage heterogeneity in the mammary gland and breast cancer

Sep 22, 2026

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Macrophages are innate immune cells with extensive phenotypic and functional plasticity, shaping tissue development, homeostasis, and cancer. This review analyzes heterogeneity among tissue-resident macrophages in the normal mammary gland and tumor-associated macrophages in breast cancer. Tissue-resident subsets support mammary development via extracellular matrix remodeling, apoptotic clearance, and cellular crosstalk. In cancer, tumor-associated macrophages drive growth and metastasis through matrix remodeling, angiogenesis, lymphangiogenesis, and immunosuppression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Introduction

Method

Results

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DOI: 10. 1002/cam4 .7053 REVIEW Defining and targeting macrophage heterogeneity in the mammary gland and breast cancer Alexis K. Elfstrum1 | Aditi S. Bapat2 | Kathryn L. Schwertfeger3,4,5 1Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, Minnesota, USA 2Molecular Pharmacology and Therapeutics Graduate Program, University of Minnesota, Minneapolis, Minnesota, USA 3Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA 4Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA 5Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA Correspondence Kathryn L. Schwertfeger, Department of Laboratory Medicine and Pathology, University of Minnesota, 2231 6 St SE, Minneapolis, MN 55455, USA. Email: [schwe251@umn.edu](schwe251@umn.edu) Funding information National Cancer Institute, Grant/ Award Number: R01CA215052 and R01CA265004; National Institute of Child Health and Human Development, Grant/Award Number: R01HD106929 and R01HD95858 Abstract Introduction: Macrophages are innate immune cells that are associated with extensive phenotypic and functional plasticity and contribute to normal development, tissue homeostasis, and diseases such as cancer. In this review, we discuss the heterogeneity of tissue resident macrophages in the normal mammary gland and tumor‐associated macrophages in breast cancer. Tissue resident macrophages are required for mammary gland development, where they have been implicated in promoting extracellular matrix remodeling, apoptotic clearance, and cellular crosstalk. In the context of cancer, tumor‐associated macrophages are key drivers of growth and metastasis via their ability to promote matrix remodeling, angiogenesis, lymphangiogenesis, and immunosuppression. Method: We identified and summarized studies in Pubmed that describe the phenotypic and functional heterogeneity of macrophages and the implications of targeting individual subsets, specifically in the context of mammary gland development and breast cancer. We also identified and summarized recent studies using single-cell RNA sequencing to identify and describe macrophage subsets inhuman breast cancer samples. Results: Advances in single‐cell RNA sequencing technologies have yielded nuances in macrophage heterogeneity, with numerous macrophage subsets identified in both the normal mammary gland and breast cancer tissue. Macrophage subsets contribute to mammary gland development and breast cancer progression in differing ways, and emerging studies highlight a role for spatial localization in modulating their phenotype and function. Conclusion: Understanding macrophage heterogeneity and the unique functions of each subset in both normal mammary gland development and breast cancer progression may lead to more promising targets for the treatment of breast cancer. KEYWORDS breast cancer, LYVE-1, macrophage, mammary gland, TREM2 | Alexis K. Elfstrum and Aditi S. Bapat contributed equally. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. | Cancer Medicine. 2024;00:e7053 . [https://doi.org/10.1002/cam4.7053](https://doi.org/10.1002/cam4.7053) [wileyonlinelibrary.com/journal/cam4](wileyonlinelibrary.com/journal/cam4) 1 of 19 1 | INTRODUCTION Macrophages are innate immune cells that were first reported atthe end ofthe nineteenth century and were initially definedbased on their phagocyticfunctions.1 However, more recent studies have revealed thatwhile phagocytosis remains a key function of macrophages, these cells are involved in numerous additional biological processes that include driving inflammation in response to infiltrating pathog

FAQs

What is the focus of this review?

The review focuses on macrophage heterogeneity in the normal mammary gland and in breast cancer, emphasizing how different subsets contribute to distinct functions and disease progression.

How do tumor-associated macrophages support breast cancer progression?

They promote tumor growth and metastasis by enabling extracellular matrix remodeling, angiogenesis, lymphangiogenesis, and immunosuppression.

What approaches are used to identify macrophage subsets?

The review summarizes studies from PubMed describing phenotypic and functional heterogeneity, and it also highlights recent single-cell RNA sequencing work to characterize macrophage subsets in human breast cancer samples.

Sep 22, 2026

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