Human breast cancer cells educate macrophages toward the M2 activation status

摘要: The immune system plays a major role in cancer progression. In solid tumors, 5-40 % of the tumor mass consists tumor-associated macrophages (TAMs) and there is usually correlation between number TAMs poor prognosis, depending on type. resemble M2 macrophages. Unlike M1-macrophages which have pro-inflammatory anti-cancer functions, M2-macrophages are immunosuppressive, contribute to matrix-remodeling, hence favor growth. not fully understood breast Macrophage infiltration (CD68) activation status (HLA-DRIIα, CD163) were evaluated large cohort human primary tumors (562 tissue microarray samples), by immunohistochemistry scored automated image analysis algorithms. Survival groups was compared using Kaplan-Meier life-table method Cox multivariate proportional hazards model. education cells assessed ex vivo differentiation peripheral blood mononuclear (PBMCs) presence or absence cell conditioned media (MDA-MB231, MCF-7 T47D lines) M1 inducing cytokines (respectively IFN-γ, IL-4 IL-10). Obtained analyzed flow cytometry (CD14, CD16, CD64, CD86, CD200R CD163), ELISA (IL-6, IL-8, IL-10, monocyte colony stimulating factor M-CSF) zymography (matrix metalloproteinase 9, MMP-9). Clinically, we found that high numbers CD163+ strongly associated with fast proliferation, differentiation, estrogen receptor negativity histological ductal type (p<0.001) studied tumors. We demonstrated cell-secreted factors modulate macrophage toward phenotype. Furthermore, more aggressive mesenchymal-like line MDA-MB231, secretes levels M-CSF, skews immunosuppressive M2c subtype. This study demonstrates influence TAM correlates recurrence free survival, thus further emphasizing can similarly affect therapy efficacy patient outcome.