TY - JOUR
T1 - A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity
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
N1 - Publisher Copyright:
© 2019, American Society for Clinical Investigation.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85072791742&partnerID=8YFLogxK
U2 - 10.1172/JCI127590
DO - 10.1172/JCI127590
M3 - Article
C2 - 31449054
AN - SCOPUS:85072791742
SN - 0021-9738
VL - 129
SP - 4151
EP - 4164
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 10
ER -
