TUMOR-ASSOCIATED MACROPHAGES: RELATIONSHIP WITH CLINICAL STATUS OF PATIENTS AND MOLECULAR BIOLOGICAL FEATURES OF BREAST CANCER.

Abstract

Background: Infiltration of the tumor microenvironment by macrophages plays a key role in the progression of breast cancer (BC), modulating tumor growth, angiogenesis, immunosuppression, and metastasis. However, the association between macrophage infiltration levels and the clinicopathological characteristics of BC, including the molecular subtype of the neoplasm and receptor status, remains insufficiently studied.

Aim: To investigate the relationship between macrophage infiltration in BC tissue and the extent of tumor spread as well as the molecular profile of the neoplasms.

Materials and methods: Using immunohistochemistry, the level of infiltration of tumor tissue by CD68+ (total macrophages) and CD163+ (M2 phenotype macrophages) tumor-associated macrophages (TAMs) was assessed in the postoperative samples from 67 patients with BC stage I-II.

Results: The level of CD68+ macrophage infiltration in BC tissue was associated with the disease stage (p = 0.004), tumor size (T category) (p = 0.026), and the presence of metastases in regional lymph nodes (p = 0.047). The highest number of CD163+ M2-like macrophages was recorded in poorly differentiated BC tissue (p = 0.024) and in neoplasms of the basal-like molecular subtype (p = 0.023). The lowest numbers of both CD68+ and CD163+ macrophages were detected in HER2/neu-positive tumors (p = 0.023). The data indicated that BC tumors classified as T2 and N1-N3 were characterized by an increased content of M1-polarized macrophages, whereas in basal-like BC and poorly differentiated tumors (G3), the M2 macrophage subpopulation predominated. This contributed to the formation of an immunosuppressive tumor phenotype and indicated the potential prognostic significance of macrophage infiltration in malignant breast neoplasms.

Conclusions: The topology and quantitative characteristics of macrophage infiltration in tumor tissue are closely associated with the extent of BC spread and the molecular profile of the neoplasms. The CD68+/CD163+ cell ratio may reflect the balance between antitumor and immunosuppressive mechanisms within the microenvironment and be considered a potential prognostic marker.