Suzuki Eiji, Kataoka Tatsuki R, Hirata Masahiro, Kawaguchi Kosuke, Nishie Mariko, Haga Hironori, Toi Masakazu
Department of Breast Surgery, Kyoto University Hospital, 54 Shogoin kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Diagnostic Pathology, Kyoto University Hospital, 54 Shogoin kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
BMC Cancer. 2015 Feb 6;15:39. doi: 10.1186/s12885-015-1041-3.
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; 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).
To 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.
HER2 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.
HER2-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.
噬细胞作用被定义为细胞表面膜蛋白和膜片通过接触从一个细胞转移到另一个细胞。据报道，人表皮生长因子受体2（HER2）可通过噬细胞作用从癌细胞转移至单核细胞；然而，其临床意义尚不清楚。本研究的目的是证实接受曲妥珠单抗为主的新辅助全身治疗（PST）的HER2过表达（HER2+）乳腺癌患者中HER2（+）肿瘤浸润免疫细胞（通过HER2噬细胞作用产生）的存在并评估其临床意义。
为评估HER2从癌细胞到免疫细胞的噬细胞作用，并评估HER2在免疫细胞和癌细胞上的上调和下调情况，分别将健康志愿者和乳腺癌患者的外周血单个核细胞与有或无曲妥珠单抗的HER2+和HER2阴性乳腺癌细胞系共培养。分析接受曲妥珠单抗为主的PST治疗的HER2+乳腺癌患者中肿瘤浸润免疫细胞上HER2表达与病理完全缓解（pCR）之间的相关性。
HER2通过噬细胞作用从HER2+乳腺癌细胞转移至单核细胞和自然杀伤细胞。曲妥珠单抗介导的经噬细胞作用的HER2（+）效应细胞比未发生HER2噬细胞作用的效应细胞表现出更高的CD107a表达。在乳腺癌患者中，未经治疗的HER2+肿瘤中肿瘤浸润免疫细胞上的HER2表达与曲妥珠单抗为主的PST治疗后的pCR相关。
HER2噬细胞作用是癌细胞与免疫细胞之间肿瘤微环境相互作用的明显证据。鉴于这些细胞之间的有效接触对于靶癌细胞的免疫破坏至关重要，这种相互作用具有重要意义。HER2噬细胞作用有可能作为HER2（+）乳腺癌患者曲妥珠单抗为主的PST疗效的预测生物标志物。
