Abstract
Monocarboxylate transporter 1 (MCT1) participates in the transport of lactate to facilitate metabolic reprogramming during tumor progression. Tumor-associated macrophages (TAMs) are also involved in the inflammatory adaptation of the tumor microenvironment (TME). This study aimed to determine the correlation between metabolite changes and the polarization of macrophages in the TME. We demonstrated that the expression of CD163 on macrophages was significantly higher in breast cancer tissues than in normal tissues, especially in the HER2 subtype, although it was not statistically associated with recurrence-free survival (RFS). The presence of MCT1+ and CD163+ macrophages in the invasive margin was significantly correlated with decreased RFS. A significant correlation existed between MCT1 and CD163 expression in the margin, and high infiltration of MCT1+CD163+ macrophages into the margin predicted rapid progression and poor survival outcomes for breast cancer patients. These data suggested that MCT1 at least partially promoted the alternative polarization of macrophages to inhibit antitumor immunity, and blocking this interaction may be a promising method for breast cancer therapy.
Highlights
The tumor microenvironment (TME) is a heterogeneous ecosystem, including infiltrating immune cells, mesenchymal support cells, and matrix components [1]
Our results demonstrated that compared with low expression of CD163Margin, high expression of CD163Margin was significantly associated with larger tumor size (p = 0.005), lymph node metastasis (p = 0.005), PR status (p = 0.006), and higher Ki67 (p = 0.002), which indicated that CD163Margin might be a predictor of prognosis for breast cancer patients
Tumor-associated macrophages are important cells involved in the tumor microenvironment and participate in tumor progression, immune suppression, metastasis, and tumor angiogenesis through cross-talk with tumor cells and other stromal cells
Summary
The tumor microenvironment (TME) is a heterogeneous ecosystem, including infiltrating immune cells, mesenchymal support cells, and matrix components [1]. With the metabolic and inflammatory reprogramming of tumor cells during cancer progression, the TME is converted into an advantageous microenvironment with altered generation of metabolites, such as lactate, pyruvate and ketone bodies, and adaptive infiltration of tumor-infiltrating lymphocytes. M1 macrophages are thought to be proinflammatory and are characterized by high expression of proinflammatory factors, such as interleukin (IL)-12, nitric oxide synthase 2 (NOS2), and tumor necrosis factor (TNF)-α. The pan-macrophage marker CD68 is generally utilized to identify tumor-associated macrophages (TAMs) in diagnostic biopsy samples, and CD163 and CD206 are used to identify M2 macrophages [3]
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