Tumor immune microenvironment and systemic response in breast cancer

Cancer immunotherapies, particularly immune checkpoint inhibitors (ICIs) that target programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1), have revolutionized cancer treatment. ICIs are effective against breast cancer, and their efficacy against triple-negative breast cancer (TNBC) has been reported. The efficacy of immunotherapy is related to the tumor immune microenvironment. In particular, tumor-infiltrating immune cells, hypoxia, and mitochondria in the tumor microenvironment are closely associated with anti-tumor immunity. Moreover, breast cancer (BC) tumors exhibit high heterogeneity; however, identification of effective biomarkers, via tissue biopsies, is limited owing to the invasiveness of the procedure. Therefore, it is crucial to develop non-invasive protocols (e.g., blood and fecal sampling) to identify components of the tumor immune microenvironment that reflect the systemic immune response, for the characterization of immunotherapy biomarkers. Herein, we review the relationship among systemic immune responses-via liquid biopsy analysis-the microbiome, and the tumor immune microenvironment in BC, while characterizing prospective biomarkers. Relationship between TIME and systemic response in breast cancer.