A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity
| Autor: | Diana Rasoulouniriana, Ronen Brenner, Nathan E. Reticker-Flynn, Alexander Tsivian, Yariv Wine, Corey Saperia, Eiman Abu Bandora, Nadine Santana-Magal, Leen Farhat-Younis, Peleg Rider, Haim Gutman, Yaron Carmi, Amit Gutwillig, Lior Tal |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male medicine.medical_treatment Melanoma Experimental Mice Transgenic CD8-Positive T-Lymphocytes Immunotherapy Adoptive 03 medical and health sciences Mice 0302 clinical medicine Cancer immunotherapy T-Lymphocyte Subsets Cell Line Tumor medicine Cytotoxic T cell Animals Humans Receptor Mice Inbred BALB C biology Chemistry T-cell receptor Receptors IgG Antibody-Dependent Cell Cytotoxicity Mammary Neoplasms Experimental General Medicine Immunotherapy Th1 Cells Acquired immune system Mice Inbred C57BL 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis Cancer research biology.protein Female Antibody CD8 Research Article |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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