Vitamin D3 reduces the expression of M1 and M2 macrophage markers in breast cancer patients

Vitamin D₃ (VD) is known for its immunomodulatory and anticancer effects. This study aimed to characterize tumor-associated macrophages (TAMs) in breast cancer (BC) and assess the influence of VD and its active metabolite, calcitriol, on their polarization. TAMs were isolated from BC patients and characterized. Monocytes were differentiated into macrophage classes (M0, M1, M2a, M2c) and treated ex vivo with calcitriol. The expression of VD-related proteins in tumor tissue was correlated with TAMs and monocyte-derived macrophages (MDMs) characteristics. TAM expression of CD200R, CD204, CD80, HLA-DR, and CD44 was negatively correlated with CYP27B1 in selected patient groups. Patients with high CYP27B1 tumor expression showed significantly lower CD200R, CD204, and CD44 expression. In patients with normal VD levels and premenopausal, CD80 expression in M2a and M2c MDMs (control, untreated ex vivo with calcitriol) was negatively correlated with plasma VD. Calcitriol reduced HLA-DR during MDM differentiation in all patients; CD80 decrease significantly except in patients with normal VD levels or metastasis. Calcitriol also decreased CD163 expression. The decrease in both M1 and M2 macrophage markers by calcitriol or their negative correlation with CYP27B1 indicate the modulatory, but rather anticancer activity of VD. The intensity of these effects was the strongest in postmenopausal patients and those without metastases.