Roles of macrophages and monocytes in resistance to immunotherapy in breast cancers.

Abstract

Immunotherapy is increasingly integral to breast cancer treatment, yet a subset develops resistance, partly mediated by macrophages and monocytes in the tumor immune microenvironment. While macrophages play essential roles in phagocytosis and pathogen clearance, their dual role in breast cancer-acting as both barriers to therapy and potential therapeutic targets-complicates treatment efficacy. Tumor-associated macrophages, polarized by tumor-derived signals, promote cancer progression and metastasis. Monocytes, subdivided into CD14+CD16- and CD14+CD16+ subsets, exhibit distinct functional profiles in cytokine secretion, antigen presentation, and migration. Modulating monocyte subset dynamics and functionality may enhance immunotherapy responsiveness. A multimodal strategy targeting macrophages, monocytes, and complementary immunotherapies offers promising avenues to overcome resistance. Further research into the heterogeneity and regulatory mechanisms of these cells is critical for developing optimized, safe immunotherapeutic protocols. This review underscores the necessity of combination immunotherapies to improve outcomes in breast cancer.