A Novel Subset of CD4+ T Cell Expressing the High Affinity Fcγ Receptor Links Antibody and T Cell Immunity

While CD4+ cells are known to associate with improved tumor prognosis, their main role is attributed to supporting the cytotoxic activity of CD8+ T cells and macrophages. 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 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 infecting conventional CD4+ T with FcγRI and its signaling chain, we successfully employed this mechanism to treat established solid cancers. Overall, this discovery shed new light on the biology of this previously unknown T cell subset, their function during tumor immunity and open a new venue to utilize their unique killing signals in immunotherapy.