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PP-21

Mechanisms of CD070, an active compound from Chinese herbal medicine,

in regulating and inhibiting PD-1 expression

#,1
Ping Chen, Hung-Rong Yen 1,2,3 Ying-Chyi Song* ,1,2,4

1 College of Chinese Medicine, China Medical University, Taichung, Taiwan.
2 Research Center for Traditional Chinese Medicine, Department of Medical Research, China
Medical University Hospital, Taichung, Taiwan.
3 Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.
4 Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
* E-mail: songyingchyi@gmail.com

Abstract
Despite the clinical success of PD-1 antibodies in cancer treatment, their limitations—such
as low response rates across tumor types, immune-related adverse events, and high cost—
highlight the need for alternative therapeutic strategies. From a clinical perspective, there is an
urgent need to develop additional therapeutic agents targeting PD-1, not only through the
inhibition of its downstream signaling pathways but also by directly downregulating its
expression. This study aims to identify compounds that directly suppress PD-1 expression on T
cells and explore their mechanism. We investigated CD070, a bioactive compound from
Chinese herbal medicine, which exhibits anti-tumor, antioxidant, anti-fibrotic, and anti-
inflammatory properties. Our results demonstrated that CD070 significantly downregulated
PD-1 protein expression in Jurkat cells. In peripheral blood mononuclear cells (PBMCs) from
three donors, CD070 treatment also led to decreased PD-1 expression in CD3⁺, CD4⁺, and CD8⁺
T cell populations. Notably, Seahorse extracellular acidification rate (ECAR) analysis revealed
that CD070 inhibited glycolysis of T cells in a dose-dependent manner. Consistently, 2-
deoxyglucose (2-DG), a glycolysis inhibitor, similarly downregulated PD-1 expression.
Furthermore, increasing glucose concentrations in glucose-free culture medium enhanced PD-
1 expression, further supporting the connection between glucose metabolism and immune
checkpoint regulation. Collectively, these findings suggest that CD070 suppresses PD-1
expression by modulating glycolytic activity in T cells, offering a novel metabolic-based
approach for improving the efficacy of cancer immunotherapy.

Keywords: PD-1; Chinese herbal Medicine; T cell; Glycolysis; Cancer immunotherapy