A distinct subset of Th1 cells express the high-affinity Fcγ receptor and exert antibody-mediated cytotoxic activity in solid tumors

While a high frequency of T helper 1 (Th1) cells in tumors is associated with improved cancer prognosis, this benefit has been attributed to supporting the cytotoxic activity of CD8⁺ T cells and macrophages. In studies of the effect of T cells on 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 FcγR 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 FcgRI 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 previously unknown T cell subset, their function during tumor immunity and their potential use in immunotherapy.