Tumor-associated Macrophages: Unwitting Accomplices in Breast Cancer Malignancy

Overview

Journal NPJ Breast Cancer

Date 2016 Mar 22

PMID 26998515

Citations 242

Authors

Carly Bess Williams

Elizabeth S Yeh

Adam C Soloff

Affiliations

Soon will be listed here.

Abstract

Deleterious inflammation is a primary feature of breast cancer. Accumulating evidence demonstrates that macrophages, the most abundant leukocyte population in mammary tumors, have a critical role at each stage of cancer progression. Such tumor-associated macrophages facilitate neoplastic transformation, tumor immune evasion and the subsequent metastatic cascade. Herein, we discuss the dynamic process whereby molecular and cellular features of the tumor microenvironment act to license tissue-repair mechanisms of macrophages, fostering angiogenesis, metastasis and the support of cancer stem cells. We illustrate how tumors induce, then exploit trophic macrophages to subvert innate and adaptive immune responses capable of destroying malignant cells. Finally, we discuss compelling evidence from murine models of cancer and early clinical trials in support of macrophage-targeted intervention strategies with the potential to dramatically reduce breast cancer morbidity and mortality.

Citing Articles

Stachydrine targeting tumor-associated macrophages inhibit colorectal cancer liver metastasis by regulating the JAK2/STAT3 pathway.

Gui Y, Xue G, Yuan Y, Wang J, Deng S, Gao F Front Pharmacol. 2025; 16:1514158.

PMID: 39974738 PMC: 11835834. DOI: 10.3389/fphar.2025.1514158.

GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth.

Mohamedali K, Aguirre B, Lu C, Chandla A, Kejriwal N, Liu L J Immunother Cancer. 2025; 12(12.

PMID: 39794935 PMC: 11667298. DOI: 10.1136/jitc-2024-008891.

The Therapeutic Potential of Physical Exercise in Cancer: The Role of Chemokines.

Buzaglo G, Telles G, Araujo R, Junior G, Ruberti O, Ferreira M Int J Mol Sci. 2025; 25(24.

PMID: 39769501 PMC: 11678861. DOI: 10.3390/ijms252413740.

Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review.

Serrano Garcia L, Javega B, Llombart Cussac A, Gion M, Perez-Garcia J, Cortes J Front Immunol. 2024; 15:1513421.

PMID: 39735530 PMC: 11671371. DOI: 10.3389/fimmu.2024.1513421.

Bone mineral density affects tumor growth by shaping microenvironmental heterogeneity.

Whitman M, Mantri M, Spanos E, Estroff L, De Vlaminck I, Fischbach C Biomaterials. 2024; 315:122916.

PMID: 39490060 PMC: 11658005. DOI: 10.1016/j.biomaterials.2024.122916.

References

Franklin R, Liao W, Sarkar A, Kim M, Bivona M, Liu K . The cellular and molecular origin of tumor-associated macrophages. Science. 2014; 344(6186):921-5. PMC: 4204732. DOI: 10.1126/science.1252510. View

Wu X, Chen H, Parker B, Rubin E, Zhu T, Lee J . HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition. Cancer Res. 2006; 66(19):9527-34. DOI: 10.1158/0008-5472.CAN-05-4470. View

Ojalvo L, Whittaker C, Condeelis J, Pollard J . Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. J Immunol. 2009; 184(2):702-12. PMC: 3226722. DOI: 10.4049/jimmunol.0902360. View

de Palma M, Venneri M, Galli R, Sergi Sergi L, Politi L, Sampaolesi M . Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell. 2005; 8(3):211-26. DOI: 10.1016/j.ccr.2005.08.002. View

Koebel C, Vermi W, Swann J, Zerafa N, Rodig S, Old L . Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007; 450(7171):903-7. DOI: 10.1038/nature06309. View

Beatty G, Chiorean E, Fishman M, Saboury B, Teitelbaum U, Sun W . CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011; 331(6024):1612-6. PMC: 3406187. DOI: 10.1126/science.1198443. View

Hashimoto D, Chow A, Noizat C, Teo P, Beasley M, Leboeuf M . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013; 38(4):792-804. PMC: 3853406. DOI: 10.1016/j.immuni.2013.04.004. View

Panni R, Linehan D, DeNardo D . Targeting tumor-infiltrating macrophages to combat cancer. Immunotherapy. 2013; 5(10):1075-87. PMC: 3867255. DOI: 10.2217/imt.13.102. View

Chen Q, Zhang X, Massague J . Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell. 2011; 20(4):538-49. PMC: 3293160. DOI: 10.1016/j.ccr.2011.08.025. View

10.

Tanaka M, Ikeda K, Suganami T, Komiya C, Ochi K, Shirakawa I . Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis. Nat Commun. 2014; 5:4982. DOI: 10.1038/ncomms5982. View

11.

Lin E, Nguyen A, Russell R, Pollard J . Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 2001; 193(6):727-40. PMC: 2193412. DOI: 10.1084/jem.193.6.727. View

12.

Deckers M, van Dinther M, Buijs J, Que I, Lowik C, van der Pluijm G . The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res. 2006; 66(4):2202-9. DOI: 10.1158/0008-5472.CAN-05-3560. View

13.

Jassar A, Suzuki E, Kapoor V, Sun J, Silverberg M, Cheung L . Activation of tumor-associated macrophages by the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid induces an effective CD8+ T-cell-mediated antitumor immune response in murine models of lung cancer and mesothelioma. Cancer Res. 2005; 65(24):11752-61. DOI: 10.1158/0008-5472.CAN-05-1658. View

14.

Qian B, Pollard J . Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51. PMC: 4994190. DOI: 10.1016/j.cell.2010.03.014. View

15.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

16.

Ojalvo L, King W, Cox D, Pollard J . High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am J Pathol. 2009; 174(3):1048-64. PMC: 2665764. DOI: 10.2353/ajpath.2009.080676. View

17.

McAllister S, Weinberg R . The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014; 16(8):717-27. PMC: 6220424. DOI: 10.1038/ncb3015. View

18.

DeNardo D, Barreto J, Andreu P, Vasquez L, Tawfik D, Kolhatkar N . CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009; 16(2):91-102. PMC: 2778576. DOI: 10.1016/j.ccr.2009.06.018. View

19.

Stockmann C, Doedens A, Weidemann A, Zhang N, Takeda N, Greenberg J . Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature. 2008; 456(7223):814-8. PMC: 3103772. DOI: 10.1038/nature07445. View

20.

Mantovani A, Biswas S, Galdiero M, Sica A, Locati M . Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2012; 229(2):176-85. DOI: 10.1002/path.4133. View