Tissue-resident macrophages are major tumor-associated macrophage resources, contributing to early TNBC development, recurrence, and metastases

The role of mammary gland tissue-resident macrophages (MGTRMs) in the development of TNBC breast tumors and recurrence after surgery and chemotherapy is investigated. Triple-negative breast cancer (TNBC) is an aggressive and highly heterogenous disease with no well-defined therapeutic targets. Treatment options are thus limited and mortality is significantly higher compared with other breast cancer subtypes. Mammary gland tissue-resident macrophages (MGTRMs) are found to be the most abundant stromal cells in early TNBC before angiogenesis. We therefore aimed to explore novel therapeutic approaches for TNBC by focusing on MGTRMs. Local depletion of MGTRMs in mammary gland fat pads the day before TNBC cell transplantation significantly reduced tumor growth and tumor-associated macrophage (TAM) infiltration in mice. Furthermore, local depletion of MGTRMs at the site of TNBC resection markedly reduced recurrence and distant metastases, and improved chemotherapy outcomes. This study demonstrates that MGTRMs are a major TAM resource and play pivotal roles in the growth and malignant progression of TNBC. The results highlight a possible novel anti-cancer approach targeting tissue-resident macrophages.

Automated summary

This study investigates the role of mammary gland tissue-resident macrophages (MGTRMs) in the development of TNBC breast tumors and recurrence after surgery and chemotherapy. The findings suggest that MGTRMs are a major TAM resource and play pivotal roles in the growth and malignant progression of TNBC. Depletion of MGTRMs shows potential as a novel anti-cancer approach targeting tissue-resident macrophages.