Tumor-associated macrophages correlate with neoangiogenesis and poor outcome in vulvar squamous cell carcinoma
20 September 2018 (online)
Vulvar squamous cell cancer (VSCC) is rare, but number of cases are rising. For early stage disease, surgery is the main therapy. In metastatic or recurrent disease new treatment modalities are needed. We known, that tumor microenvironment plays a crucial role in tumor progression. Aim of our study was to analyze, if the presence of peri- and intratumor immunocytes has an impact on the course of the disease and the clinical outcome.
Primary VSCC samples of 49 patients were immunohistochemically screened for the presence of CD3+ T-cells, Foxp3+ regulatory T cells, CD68+ monocytes/macrophages and CD163+ tumor-associated macrophages (TAMs). Correlation analysis with clinicopathological parameters was performed. Additionally, macrophages were generated from buffy coat-derived peripheral blood mononuclear cells of healthy donors and analyzed for their antigen expression and cytokine/chemokine secretion after incubation with cells and supernatant of the A431 vulvar cancer cell line.
Substantial frequencies of immunocytes analyzed were detected in all VSCC specimens, both within the tumor epithelium and the underlying stroma. However, only increased stromal infiltration with TAMs correlated with higher lymph vessel density, lymph vessel invasion and poor clinical outcome. Our in vitro analyses suggest that this is due to a high VEGF secretion of TAMs as well as of tumor-cells in the presence of TAMs.
Our results show that the presence of TAMs in VSCC indicates aggressive tumor behavior. Targeting TAMs might help improving the outcome of women with locally advanced, metastatic or recurrent VSCC in the future.