Abstract
BackgroundTrogocytosis is defined as the transfer of cell-surface membrane proteins and membrane patches from one cell to another through contact. It is reported that human epidermal growth factor receptor 2 (HER2) could be transferred from cancer cells to monocytes via trogocytosis; however, the clinical significance of this is unknown. The aim of this study is to demonstrate the presence and evaluate the clinical significance of HER2+ tumor-infiltrated immune cells (arising through HER2 trogocytosis) in HER2-overexpressing (HER2+) breast cancer patients receiving trastuzumab-based primary systemic therapy (PST).MethodsTo assess the trogocytosis of HER2 from cancer cells to immune cells, and to evaluate the up- and down-regulation of HER2 on immune and cancer cells, peripheral blood mononuclear cells from healthy volunteers and breast cancer patients were co-cultured with HER2+ and HER2-negative breast cancer cell lines with and without trastuzumab, respectively. The correlation between HER2 expression on tumor-infiltrated immune cells and a pathological complete response (pCR) in HER2+ breast cancer patients treated with trastuzumab-based PST was analyzed.ResultsHER2 was transferred from HER2+ breast cancer cells to monocytes and natural killer cells by trogocytosis. Trastuzumab-mediated trogocytosed-HER2+ effector cells exhibited greater CD107a expression than non-HER2-trogocytosed effector cells. In breast cancer patients, HER2 expression on tumor-infiltrated immune cells in treatment naïve HER2+ tumors was associated with a pCR to trastuzumab-based PST.ConclusionsHER2-trogocytosis is visible evidence of tumor microenvironment interaction between cancer cells and immune cells. Given that effective contact between these cells is critical for immune destruction of target cancer cells, this interaction is of great significance. It is possible that HER2 trogocytosis could be used as a predictive biomarker for trastuzumab-based PST efficacy in HER2+ breast cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1041-3) contains supplementary material, which is available to authorized users.
Highlights
Trogocytosis is defined as the transfer of cell-surface membrane proteins and membrane patches from one cell to another through contact
Trogocytosis is observed in human epidermal growth factor receptor 2 (HER2)+ breast cancer cell lines and CD14+ cells exhibited a greater degree of trogocytosis than CD56+ cells in in vitro trogocytosis assays Initially, we performed a trogocytosis assay to determine whether trastuzumab-mediated trogocytosis occurred in HER2+ breast cancer cells
The results indicated that the CD14+ cell HER2-trogocytosis observed in Figure 1A was abrogated in a normal human plasma dose-dependent manner (Figure 1B)
Summary
Trogocytosis is defined as the transfer of cell-surface membrane proteins and membrane patches from one cell to another through contact. It is reported that human epidermal growth factor receptor 2 (HER2) could be transferred from cancer cells to monocytes via trogocytosis; the clinical significance of this is unknown. The aim of this study is to demonstrate the presence and evaluate the clinical significance of HER2+ tumor-infiltrated immune cells (arising through HER2 trogocytosis) in HER2-overexpressing (HER2+) breast cancer patients receiving trastuzumab-based primary systemic therapy (PST). The IC and small membrane fragments of the target cell, which surround the IC, are transferred to the effector cell, resulting in reduced HER2 expression on the target cell surface This phenomenon is broadly defined as trogocytosis [1], the original definition of trogocytosis, as reported by Griffin et al, referred to the transfer of IC caps from the surface of lymphocytes to macrophages.
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