Imprinting of Lymphocytes with Melanoma Antigens Acquired by Trogocytosis Facilitates Identification of Tumor-Reactive T Cells
Imprinting of Lymphocytes with Melanoma Antigens Acquired by Trogocytosis Facilitates Identification of Tumor-Reactive T Cells
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DOI：
10.4049/jimmunol.1202879
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发表时间：
2013-06-01
影响因子：
4.4
通讯作者：
Lotem, Michal
中科院分区：
文献类型：
--
作者：
Eisenberg, Galit;Uzana, Ronny;Lotem, Michal
Trogocytosis 是膜碎片和相关分子从 APC 到效应淋巴细胞的接触依赖性细胞间转移。我们之前证明，肿瘤靶标和同源黑色素瘤 Ag 特异性细胞毒性 T 细胞 (CTL) 之间也会发生 trogocytosis。在这项研究中，我们发现，在吞噬作用之后，免疫效应细胞获得了肿瘤的分子成分，包括表面抗原，这些成分可以通过特定的单克隆抗体检测到。我们证明，来自黑色素瘤患者 PBMC 和肿瘤浸润淋巴细胞 (TIL) 的 CD8(+) 和 CD4(+) T 细胞捕获黑色素瘤 Ag，从而能够通过 Ag 特异性抗体染色来识别 trogocytosing 淋巴细胞。这一发现规避了肿瘤预标记的必要性，而在过去，肿瘤预标记是检测膜捕获 T 细胞所必需的。通过检测 TIL 上的黑色素瘤 Ag，我们对 trogocytosing T 细胞进行了分选，并验证了它们的优先反应性和细胞毒性。此外，从肿瘤中提取后不久，在新鲜 TIL 培养物中以低频率检测到肿瘤 Ag 印迹 T 细胞。因此，肿瘤 Ag 的 T 细胞印记可能允许富集黑色素瘤 Ag 特异性 T 细胞，用于研究，甚至可能用于癌症患者的过继免疫治疗。免疫学杂志，2013，190：5856-5865。
Trogocytosis is a contact-dependent intercellular transfer of membrane fragments and associated molecules from APCs to effector lymphocytes. We previously demonstrated that trogocytosis also occurs between tumor target and cognate melanoma Ag-specific cytotoxic T cells (CTL). In this study, we show that, following trogocytosis, immune effector cells acquire molecular components of the tumor, including surface Ags, which are detectable by specific mAbs. We demonstrate that CD8(+) and CD4(+) T cells from melanoma patients' PBMC and tumor-infiltrating lymphocytes (TIL) capture melanoma Ags, enabling identification of trogocytosing lymphocytes by staining with Ag-specific Abs. This finding circumvents the necessity of tumor prelabeling, which in the past was mandatory to detect membrane-capturing T cells. Through the detection of melanoma Ags on TIL, we sorted trogocytosing T cells and verified their preferential reactivity and cytotoxicity. Furthermore, tumor Ag imprinted T cells were detected at low frequency in fresh TIL cultures shortly after extraction from the tumor. Thus, T cell imprinting by tumor Ags may allow the enrichment of melanoma Ag-specific T cells for research and potentially even for the adoptive immunotherapy of patients with cancer. The Journal of Immunology, 2013, 190: 5856-5865.