title: Human T cell crosstalk is induced by tumor membrane transfer.
abstract: Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC). Previously, we have demonstrated that trogocytosis also takes place between melanoma-specific cytotoxic T lymphocytes (CTLs) and their cognate tumors. In the present study, we took this finding a step further, focusing on the ability of melanoma membrane-imprinted CD8+ T cells to act as APCs (CD8+ T-APCs). We demonstrate that, following trogocytosis, CD8+ T-APCs directly present a variety of melanoma derived peptides to fraternal T cells with the same TCR specificity or to T cells with different TCRs. The resulting T cell-T cell immune synapse leads to (1) Activation of effector CTLs, as determined by proliferation, cytokine secretion and degranulation; (2) Fratricide (killing) of CD8+ T-APCs by the activated CTLs. Thus, trogocytosis enables cross-reactivity among CD8+ T cells with interchanging roles of effectors and APCs. This dual function of tumor-reactive CTLs may hint at their ability to amplify or restrict reactivity against the tumor and participate in modulation of the anti-cancer immune response.
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Ronny
authors: R
authors: Uzana
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Galit
authors: G
authors: Eisenberg
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Sharon
authors: S
authors: Merims
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Shoshana
authors: S
authors: Frankenburg
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Aviad
authors: A
authors: Pato
authors: Lautenberg Center for General and Tumor Immunology, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors: Eitan
authors: E
authors: Yefenof
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Roni
authors: R
authors: Engelstein
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Tamar
authors: T
authors: Peretz
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Arthur
authors: A
authors: Machlenkin
authors: Sharett Institute of Oncology, Hadassah Medical Organization, P.O. Box 12000, Jerusalem 91120, Israel.
authors: Michal
authors: M
authors: Lotem
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II