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Updated: Dec 27, 2025

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
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GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

Choong-Hyun Koh1, Il-Kyu Kim1,2, Kwang-Soo Shin1

  • 1Laboratory of Immunology, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.

Cancer Immunology Research
|March 4, 2020
PubMed

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.

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