Page 327 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

TC-12

Suppression of triple-negative breast cancer growth by the

immunomodulatory glycolipids

1
#,1
1,2
Yi-Hsiang Wang, Meng-Ting Chang, Yi-Fan Chen, Qu-Xuan Wu, Yi-Ting Wang,
1,2
1
Juimin Chang Lie-Fen Shyur,* ,1,2 Tai-Na Wu*
,1,2
1

1 Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan
2 Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan
* E-mail: taina@gate.sinica.edu.tw

Abstract
Natural killer T (NKT) cells recognize glycolipids presented by the CD1d molecule on
dendritic cells (DCs). Upon stimulation, NKT cells produce large amounts of cytokines that
activate other immune cells, thereby triggering anticancer responses. Plant-derived glycolipids
with the potential to activate NKT cells may provide an alternative choice for the treatment of
triple-negative breast cancer (TNBC) patients, because targeted therapies such as trastuzumab
and hormonal drugs cannot be used. The immunomodulatory activities of the glycolipid (G)
and its enriched fraction (A) were investigated in bone marrow-derived DCs (BMDCs) and the
DC-T coculture system in vitro. Flow cytometry and enzyme-linked immunosorbent assay
(ELISA) were used to evaluate the activation status of immune cells in vivo. G/A could activate
DCs to upregulate CD40 and CD86 and to produce IL-12. G/A also stimulated conventional T
and NKT cells to secrete interferon (IFN)-γ, but not IL-4, in vitro. The ratio of TNF-α to IL-4
was significantly increased in the serum of A-treated mice. In the tumor microenvironment
(TME), A induced DC to secrete IL-12 and stimulated T and NKT cell activation. However,
only NKT cells showed a lower degree of exhaustion in the spleen and TME of tumor-bearing
mice, leading to suppression of tumor growth in WT mice but not in NKT knockout mice. These
results suggested that NKT cells were the major effector cells mediating A-induced anticancer
effects. In conclusion, plant-derived glycolipids activated DCs and NKT cells and stimulated
Th1-directed cytokine production, which together contribute to A-induced anticancer activities.

Keywords: Glycolipid; NKT; DC; TNBC