M1 and M2 macrophage phenotypic diversity in the tumor microenvironment in breast cancer patients: association with clinical and pathological parameters

Abstract

Introduction. M1 and M2 macrophages in the tumor microenvironment are known to express programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). It can determine disease outcomes and tumor response to treatment including immunotherapy. However, the macrophage composition of the breast cancer microenvironment and its relation to various clinical and pathological features have been only partially studied. The aim of the study was to detect the PD-1 and PD-L1 expression features in M1 and M2 macrophages in breast cancer patients depending on menstruation, tumor size, molecular subtype, lymph node metastases, and hematogenous metastases. Materials and methods. The study included 19 patients with breast cancer. Using seven-color multiplex TSA-modified immunohistochemistry, we identified M1 macrophages (CD68+CD163–CD3–CKAE1/3–), M2 macrophages (CD68+/–CD163+CD3–CKAE1/3–), and PD-1 and PD-L1 expression in the macrophages. Results. The macrophage composition of the breast carcinoma microenvironment varies in PD-1 and PD-L1 expression. M1 macrophages are more characteristic to show their expression, and it does not depend on the molecular subtype and the presence of hematogenous metastases. Simultaneously, the relative number of macrophages with phenotypes PD1–PDL1+ M1 and PD1+PDL1+ M2 was higher in patients with tumor size corresponding to T2 compared to T1. Differences in macrophage composition were found in patients depending on the lymph node involvement. Patients without lymph node metastases had virtually no PD-1 expression in M2 macrophages in contrast to patients with them. Conclusion. Breast cancer was shown to have phenotypic variety of macrophages in the tumor microenvironment. Moreover, macrophage composition was diverse in different individuals. Initially, a different composition of macrophages is characteristic of patients with different tumor sizes and different lymph node involvement. Keywords: breast cancer, M1 macrophages, M2 macrophages, PD-L1, PD-1