Abstract
The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells and infiltrating immune cells, which may inhibit or promote tumor growth and progression. The objectives of this retrospective study were to characterize the density of tumor-associated macrophages (TAMs) in breast cancer, and to correlate the density of TAMs with clinicopathological parameters. Paraffin-embedded specimens and clinicopathological data, including up to 5 years follow-up information, were obtained from 172 breast cancer patients. Immunohistochemical staining for CD68 (marker for macrophages) was performed and evaluated in a blinded fashion. We found that TAMs were significantly frequent in high histopathological grade breast cancer patients. Breast cancer patients with a high density of TAMs had significantly lower rates of disease-free survival and 5-year overall survival than patients with low density of TAMs. Furthermore, high-infiltration of TAMs indicated worse survival rate for patients with node-negative breast cancer. In conclusion, the number of TAMs in the tumor stroma is an independent predictor of survival time for breast cancer patients. High-infiltration of TAMs is a significant unfavorable prognostic factor for patients with invasive breast cancer and, as such, is a potentially useful prognostic marker for breast cancer.
Highlights
The tumor microenvironment is comprised of tumor cells and heterogeneous populations of stromal cells such as fibroblasts, endothelial cells and infiltrating immune cells, as well as the products of these cells such as extracellular matrix, chemokines, cytokines, growth factors, enzymes and various metabolites [1,2]
We found no significant correlations between tumor-associated macrophages (TAMs) status and age, menopausal status, tumor size, or estrogen receptor (ER) or progesterone receptor (PR) expression
We evaluated the prognostic significance of TAMs in a large number of invasive breast carcinomas
Summary
The tumor microenvironment is comprised of tumor cells and heterogeneous populations of stromal cells such as fibroblasts, endothelial cells and infiltrating immune cells, as well as the products of these cells such as extracellular matrix, chemokines, cytokines, growth factors, enzymes and various metabolites [1,2]. The immune system of the tumor-bearing host interacts with tumors throughout their development [4], and the consequences of this interaction have substantial implications for cancer therapy Among these immune cells, tumor-associated macrophages (TAMs) are considered the most powerful inhibitors of antitumor immunity and the greatest barrier to successful immunotherapy [5]. As well as IL-10, release anti-inflammatory molecules such as IL-4, IL-13 and transforming growth factor beta[7] Both M1 and M2 can infiltrate into tumor sites, naturally arised TAMs are biased towards the M2 type and show mostly pro-tumor functions, promoting tumor progression, inducing tumor-anginogenesis and dampening anti-tumor immune response [8,9]. Catharina et al further demonstrated that the presence of TAMs in tumor stroma but not in tumor nest was an independent prognostic factor for reduced breast cancer specific survival [16]. The expression of TAMs in node-negative breast cancer has not been well documented
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