Marsdenia tenacissima enhances immune response of tumor infiltrating T lymphocytes to colorectal cancer

Ben Yi; Shuai Zhang; Suying Yan; Yanfei Liu; Zhiqiang Feng; Tianhao Chu; Jun Liu; Wei Wang; Jun Xue; Chunze Zhang; Yijia Wang

doi:10.3389/fimmu.2023.1238694

Marsdenia tenacissima enhances immune response of tumor infiltrating T lymphocytes to colorectal cancer

Front Immunol. 2023 Aug 15:14:1238694. doi: 10.3389/fimmu.2023.1238694. eCollection 2023.

Authors

Ben Yi^{1

2}, Shuai Zhang¹, Suying Yan^{1

2}, Yanfei Liu^{1

2}, Zhiqiang Feng^{1

2}, Tianhao Chu^{1

2}, Jun Liu³, Wei Wang⁴, Jun Xue⁵, Chunze Zhang², Yijia Wang⁶

Affiliations

¹ School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
³ Department of Radiology, The Fourth Central Hospital Affiliated to Nankai University, Tianjin, China.
⁴ TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China.
⁵ Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
⁶ Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Tianjin, China.

Abstract

Introduction: Tumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear.

Method: We collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors.

Results: Under single and co-culture conditions, MTE inhibited TGF-β1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models.

Conclusions: Our findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.

Keywords: CD8; colorectal cancer; marsdenia tenacissima extraction; tumor infiltrating T cells; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes
Cell Line
Colitis-Associated Neoplasms*
Immunity
Marsdenia*
Mice
Tumor Microenvironment

Grants and funding

This work was partially supported by the Natural Science Foundation of China Grant number 81972826 and 12174203, and the foundation of committee on science and technology of Tianjin under Grant number 22JCYBJC00570, 21JCYBJC00180, 21JCYBJC00120, and Key R&D Projects in the Tianjin Science and Technology Pillar Program Grant number 19YFZCSY00420, and Tianjin Key Medical Discipline (Specialty) Construction Project Grant number TJYXZDXK-044A.