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PP-17

Genipin from Gardenia jasminoides reprograms IL-17-oroducing CD8⁺ T

cells toward cytotoxic TC1-like phenotypes for enhanced anti-tumor

immunity

1
3
2
Chi-Yen Hsieh, Chuan-Teng Liu, Ying-Chyi Song, Hung-Rong Yen* ,2,4,5

1 M.D./Ph.D. program, School of Medicine, and Gradutate Institute of Biomedical Sciences,
College of Medicine, China Medical University, Taichung 404328, Taiwan
2 Research Center for Traditional Chinese Medicine, Department of Medical Research, China
Medical University Hospital, Taichung 404327, Taiwan
3 Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical
University, Taichung 404328, Taiwan
4 School of Chinese Medicine, College of Chinese Medicine, China Medical University,
Taichung 404328, Taiwan
5 Department of Chinese Medicine, China Medical University Hospital, Taichung 404327,
Taiwan
* E-mail: hungrongyen@mail.cmu.edu.tw

Abstract
IL-17-producing CD8⁺ T cells (Tc17) exhibit functional plasticity, offering potential for novel
cancer immunotherapies. While Tc17 cells are typically tumor-promoting, recent studies
indicate they can be reprogrammed into IFN-γ-producing, cytotoxic Tc1-like cells. This study
investigated whether compounds from Traditional Chinese Medicine (TCM) can modulate Tc17
phenotypes to enhance anti-tumor immunity. Polarized Tc17 cells were treated with genipin, a
natural UCP2 inhibitor derived from Gardenia jasminoides with known anti-inflammatory and
immunometabolic regulatory properties. Expression of IFN-γ, T-bet, and granzyme B was
quantified. Cytotoxicity was assessed against E.G7-OVA lymphoma cells, and metabolic
profiling was performed to explore underlying mechanisms. Genipin treatment markedly
increased IFN-γ, T-bet, and granzyme B expression in Tc17 cells. Cytotoxicity assays
confirmed enhanced tumor cell killing after treatment. Metabolic analysis suggested that
genipin-induced Tc17 reprogramming may involve metabolic rewiring. Genipin, a TCM-
derived compound, effectively reprograms Tc17 cells toward a Tc1-like cytotoxic phenotype,
enhancing anti-tumor activity. These findings support the translational potential of TCM-
derived agents in modulating pathogenic T cell subsets for cancer immunotherapy.

Keywords: Tc17; Genipin; Gardenia jasminoides; Cancer immunotherapy; Immune
metabolism