A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity

J Clin Invest. 2019 Oct 1;129(10):4151-4164. doi: 10.1172/JCI127590.


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.

Keywords: Adaptive immunity; Cancer immunotherapy; Immunology; Therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • 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
  • Receptors, IgG / metabolism*
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / classification*
  • Th1 Cells / immunology*


  • Receptors, IgG