TY - JOUR AU - Rasoulouniriana, Diana AU - Santana-Magal, Nadine AU - Gutwillig, Amit AU - Farhat-Younis, Leen AU - Wine, Yariv AU - Saperia, Corey AU - Tal, Lior AU - Gutman, Haim AU - Tsivian, Alexander AU - Brenner, Ronen AU - Bandora, Eiman Abu AU - Reticker-Flynn, Nathan E. AU - Rider, Peleg AU - Carmi, Yaron T1 - A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity PY - 2019/10/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI127590 VL - 129 IS - 10 UR - https://doi.org/10.1172/JCI127590 SP - 4151 EP - 4164 PB - The American Society for Clinical Investigation ER -