Triple-negative breast cancer influences a mixed M1/M2 macrophage phenotype associated with tumor aggressiveness

Kristine Cate S Pe; Rattana Saetung; Varalee Yodsurang; Chatchai Chaotham; Koramit Suppipat; Pithi Chanvorachote; Supannikar Tawinwung

doi:10.1371/journal.pone.0273044

Triple-negative breast cancer influences a mixed M1/M2 macrophage phenotype associated with tumor aggressiveness

PLoS One. 2022 Aug 12;17(8):e0273044. doi: 10.1371/journal.pone.0273044. eCollection 2022.

Authors

Kristine Cate S Pe¹, Rattana Saetung¹, Varalee Yodsurang¹, Chatchai Chaotham², Koramit Suppipat^{3

4}, Pithi Chanvorachote¹, Supannikar Tawinwung^{1

4}

Affiliations

¹ Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand.
² Faculty of Pharmaceutical Sciences, Department of Biochemistry and Microbiology, Chulalongkorn University, Bangkok, Thailand.
³ Faculty of Medicine, Department of Research Affair, Chulalongkorn University, Bangkok, Thailand.
⁴ Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand.

Abstract

Triple-negative breast cancer (TNBC) is characterized by excessive accumulation of tumor-infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs consist of a heterogeneous population with high plasticity and are associated with tumor aggressiveness and poor prognosis. Moreover, breast cancer cells can secrete factors that influence TAM polarization. Therefore, this study aimed to evaluate the crosstalk between cancer cells and macrophages in the context of TNBC. Cytokine-polarized M2 macrophage were used as control. Distinct from the classical M2 macrophage, TAMs generated from TNBC-conditioned media upregulated both M1- and M2-associated genes, and secreted both the anti-inflammatory cytokine interleukin IL-10 and the proinflammatory cytokine IL-6 and tumor necrosis factor- α. Theses TNBC-induced TAMs exert aggressive behavior of TNBC cells. Consistently, TCGA and MTABRIC analyses of human breast cancer revealed upregulation of M1- associated genes in TNBC comparing with non-TNBC. Among these M1-associated genes, CXCL10 and IL1B were revealed to be independent prognostic factors for disease progression. In conclusion, TNBC cells induce macrophage polarization with a mixture of M1 and M2 phenotypes. These cancer-induced TAMs further enhance tumor cell growth and aggressiveness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Proliferation
Cytokines / genetics
Humans
Macrophages
Phenotype
Triple Negative Breast Neoplasms* / pathology
Tumor Microenvironment / genetics

Substances

Cytokines

Grants and funding

ST MRG6180200 the Thailand Research Fund http://academics.trf.or.th/ No The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.