title: Imprinting of lymphocytes with melanoma antigens acquired by trogocytosis facilitates identification of tumor-reactive T cells.
abstract: 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.
authors.affiliation: Sharett Institute of Oncology, Hadassah Medical Organization, Jerusalem 91120, Israel.
authors.forename: Galit
authors.initials: G
authors.lastname: Eisenberg
authors.forename: Ronny
authors.initials: R
authors.lastname: Uzana
authors.forename: Aviad
authors.initials: A
authors.lastname: Pato
authors.forename: Shoshana
authors.initials: S
authors.lastname: Frankenburg
authors.forename: Sharon
authors.initials: S
authors.lastname: Merims
authors.forename: Eitan
authors.initials: E
authors.lastname: Yefenof
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.forename: Arthur
authors.initials: A
authors.lastname: Machlenkin
authors.forename: Michal
authors.initials: M
authors.lastname: Lotem
mesh_terms: D045744:Cell Line, Tumor; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D058950:Melanoma-Specific Antigens / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015234:HLA-A Antigens; D058950:Melanoma-Specific Antigens