Resveratrol analogue HS-1793 induces the modulation of tumor-derived T cells

Choi,Yoo Jin; Yang,Kwang Mo; Kim,Sung Dae; Yoo,Young Hyun; Lee,Sang Wha; Seo,Su Yeong; Suh,Hongsuk; Yee,Sung Tae; Jeong,Min Ho; Jo,Wol Soon

doi:10.3892/etm.2012.472

Resveratrol analogue HS-1793 induces the modulation of tumor-derived T cells

Authors:
- Yoo Jin Choi
- Kwang Mo Yang
- Sung Dae Kim
- Young Hyun Yoo
- Sang Wha Lee
- Su Yeong Seo
- Hongsuk Suh
- Sung Tae Yee
- Min Ho Jeong
- Wol Soon Jo
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Affiliations: Research Center, Dong Nam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea, Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, Republic of Korea, Department of Microbiology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, Republic of Korea, Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 609-735, Republic of Korea, Department of Biology, Sunchon National University, Sunchon, Republic of Korea
Published online on: February 3, 2012 https://doi.org/10.3892/etm.2012.472
Pages: 592-598

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Abstract

Recent advances in the understanding of the mechanisms responsible for tumor progression suggest the possibility to control cancer growth, not only through chemotherapy-induced cancer cell destruction, but also by stimulating anticancer immunity. However, immune tolerance against tumor antigens disturbs diverse forms of immunotherapy. One of the most potent and well-studied tumor-induced immunosuppressive phenotypes found in the tumor microenvironment is the regulatory subpopulation cells (CD4+CD25+FoxP3+ Treg cells). Among the great number of natural agents derived from plants and potentially useful for application in the complementary therapy of cancer, resveratrol is gaining attention for its immunomodulating properties in breast cancer, since the ineffectiveness of numerous immunotherapy strategies may be related, in part, to their negative effects on Treg cells. The present study was undertaken to examine whether HS-1793, a synthetic resveratrol analogue free from the restriction of the metabolic instability and high dose requirement of resveratrol, shows a direct effect on immune responses by enhancing lymphocyte proliferation or an immunomodulatory effect by inducing changes in the Treg cell population in FM3A breast tumor-bearing mice. Although HS-1793 had no direct immunostimulatory effect, it dose-dependently decreased IL-2 secretion and increased IL-4 secretion of concanavalin A-stimulated lymphocytes from tumor-bearing mice, which suggest that HS-1793 may induce changes in the subpopulations of tumor-derived T lymphocytes. The CD4+CD25+ cell population from tumor-bearing mice decreased after HS-1793 treatment in a dose-dependent manner, while the CD4+ T cell population remained unchanged. FoxP3+-expressing cells among the CD4+CD25+ population showed a similar pattern. In contrast, the CD8+ T cell population as well as the interferon (IFN)-γ-expressing CD8+ T cell population and IFN-γ secretion of splenocytes from tumor-bearing mice were significantly upregulated by HS-1793 treatment. These results suggest that HS-1793 induces the modulation of tumor-derived T lymphocytes, particulary having a suppressive effect on the Treg cell population, likely contributing to enhanced tumor-specific cytotoxic T lymphocyte responses and CD4+ T cells involving antitumor immunity. Therefore, HS-1793 may serve as a promising adjuvant therapeutic reagent in breast cancer immunotherapy.

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