| First Author | Koh CH | Year | 2020 |
| Journal | Cancer Immunol Res | Volume | 8 |
| Issue | 5 | Pages | 698-709 |
| PubMed ID | 32122993 | Mgi Jnum | J:318594 |
| Mgi Id | MGI:6860575 | Doi | 10.1158/2326-6066.CIR-19-0748 |
| Citation | Koh CH, et al. (2020) GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells. Cancer Immunol Res 8(5):698-709 |
| abstractText | Although treatment with the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various tumor models, the underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21-producing follicular helper T (Tfh) cells play a crucial role in DTA-1-induced tumor inhibition. The administration of DTA-1 increased IL21 expression by Tfh cells in an antigen-specific manner, and this activation led to enhanced antitumor cytotoxic T lymphocyte (CTL) activity. Mice treated with an antibody that neutralizes the IL21 receptor exhibited decreased antitumor activity when treated with DTA-1. Tumor growth inhibition by DTA-1 was abrogated in Bcl6 (fl/fl) Cd4 (Cre) mice, which are genetically deficient in Tfh cells. IL4 was required for optimal induction of IL21-expressing Tfh cells by GITR costimulation, and c-Maf mediated this pathway. Thus, our findings identify GITR costimulation as an inducer of IL21-expressing Tfh cells and provide a mechanism for the antitumor activity of GITR agonism. |
