Therapeutic potential of TNFR2 agonists: a mechanistic perspective

Yibo Chen; Mengmeng Jiang; Xin Chen

doi:10.3389/fimmu.2023.1209188

Therapeutic potential of TNFR2 agonists: a mechanistic perspective

Front Immunol. 2023 Aug 17:14:1209188. doi: 10.3389/fimmu.2023.1209188. eCollection 2023.

Authors

Yibo Chen¹, Mengmeng Jiang¹, Xin Chen^{1

2

3

4}

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, Macau SAR, China.
² Ministry of Education (MoE) Frontiers Science Center for Precision Oncology, University of Macau, Macau, Macau SAR, China.
³ Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macau, Macau SAR, China.
⁴ Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Macau, Macau SAR, China.

Abstract

TNFR2 agonists have been investigated as potential therapies for inflammatory diseases due to their ability to activate and expand immunosuppressive CD4+Foxp3+ Treg cells and myeloid-derived suppressor cells (MDSCs). Despite TNFR2 being predominantly expressed in Treg cells at high levels, activated effector T cells also exhibit a certain degree of TNFR2 expression. Consequently, the role of TNFR2 signaling in coordinating immune or inflammatory responses under different pathological conditions is complex. In this review article, we analyze possible factors that may determine the therapeutic outcomes of TNFR2 agonism, including the levels of TNFR2 expression on different cell types, the biological properties of TNFR2 agonists, and disease status. Based on recent progress in the understanding of TNFR2 biology and the study of TNFR2 agonistic agents, we discuss the future direction of developing TNFR2 agonists as a therapeutic agents.

Keywords: TNFR2; TNFR2 agonism; Treg - regulatory T cell; autoimmune diseases; tumor.

Publication types

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

MeSH terms

Immunosuppressive Agents
Myeloid-Derived Suppressor Cells*
Receptors, Tumor Necrosis Factor, Type II* / agonists
Signal Transduction
T-Lymphocytes, Regulatory

Substances

Immunosuppressive Agents
Receptors, Tumor Necrosis Factor, Type II

Grants and funding

This project has been funded by The Science and Technology Development Fund, Macau SAR (FDCT, File No. 0099/2021/A2, 0007/2022/AKP), University of Macau (File No. CPG2023-00025-ICMS, MYRG2022-00260-ICMS, SKL-QRCM(UM)-2020-2022), the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (EF006/ICMS-CX/2021/GDSTC), and the Research Institute of Tsinghua, Pearl River Delta (EF032/ICMS-CX/2021/RITH).