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A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2019 Oct 01; Vol. 129 (10), pp. 4151-4164. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Animals
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
T-Lymphocyte Subsets immunology
Antibody-Dependent Cell Cytotoxicity immunology
Receptors, IgG metabolism
Th1 Cells classification
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 129
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 31449054
- Full Text :
- https://doi.org/10.1172/JCI127590