1. A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity.
- Author
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Rasoulouniriana D, Santana-Magal N, Gutwillig A, Farhat-Younis L, Wine Y, Saperia C, Tal L, Gutman H, Tsivian A, Brenner R, Bandora EA, Reticker-Flynn NE, Rider P, and Carmi Y
- Subjects
- Animals, CD4-Positive T-Lymphocytes classification, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cell Line, Tumor, Female, HEK293 Cells, Humans, Immunotherapy, Adoptive, Male, Mammary Neoplasms, Experimental immunology, Mammary Neoplasms, Experimental therapy, Melanoma, Experimental immunology, Melanoma, Experimental therapy, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocyte Subsets immunology, Antibody-Dependent Cell Cytotoxicity immunology, Receptors, IgG metabolism, Th1 Cells classification, Th1 Cells immunology
- Abstract
While a high frequency of Th1 cells in tumors is associated with improved cancer prognosis, this benefit has been attributed mainly to support of cytotoxic activity of CD8+ T cells. By attempting to potentiate antibody-driven immunity, we found a remarkable synergy between CD4+ T cells and tumor-binding antibodies. This surprising synergy was mediated by a small subset of tumor-infiltrating CD4+ T cells that express the high-affinity Fcγ receptor for IgG (FcγRI) in both mouse and human patients. These cells efficiently lyse tumor cells coated with antibodies through concomitant crosslinking of their T cell receptor (TCR) and FcγRI. By expressing FcγRI and its signaling chain in conventional CD4+ T cells, we successfully employed this mechanism to treat established solid cancers. Overall, this discovery sheds new light on the biology of this T cell subset, their function during tumor immunity, and the means to utilize their unique killing signals in immunotherapy.
- Published
- 2019
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