Targeting toll-like receptor 7/8 for immunotherapy: recent advances and prospectives

Biomarker Research

Review

Yingmei Li¹  Yongping Song¹  Dingming Wan¹  Haizhou Xing¹  Jifeng Yu²  Hao Sun³  Song Zhao⁴  Peng Zhang⁴ 

[1] Department of Hematology, the First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;Department of Hematology, the First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;Henan International Joint Laboratory of Nuclear Protein Gene Regulation, Henan University College of Medicine, 475004, Kaifeng, Henan, China;Department of Radiotherapy, the First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;

关键词: Toll-like receptors (TLRs);    Agonist;    Immune checkpoint pathway;    cancer immunotherapy;    Chronic hepatitis B;    Clinical trial;   

DOI  :  10.1186/s40364-022-00436-7

 received in 2022-09-18, accepted in 2022-11-19,  发布年份 2022

来源: Springer

【 摘 要 】

Toll-like receptors (TLRs) are a large family of proteins that are expressed in immune cells and various tumor cells. TLR7/8 are located in the intracellular endosomes, participate in tumor immune surveillance and play different roles in tumor growth. Activation of TLRs 7 and 8 triggers induction of a Th1 type innate immune response in the highly sophisticated process of innate immunity signaling with the recent research advances involving the small molecule activation of TLR 7 and 8. The wide range of expression and clinical significance of TLR7/TLR8 in different kinds of cancers have been extensively explored. TLR7/TLR8 can be used as novel diagnostic biomarkers, progression and prognostic indicators, and immunotherapeutic targets for various tumors. Although the mechanism of action of TLR7/8 in cancer immunotherapy is still incomplete, TLRs on T cells are involved in the regulation of T cell function and serve as co-stimulatory molecules and activate T cell immunity. TLR agonists can activate T cell-mediated antitumor responses with both innate and adaptive immune responses to improve tumor therapy. Recently, novel drugs of TLR7 or TLR8 agonists with different scaffolds have been developed. These agonists lead to the induction of certain cytokines and chemokines that can be applied to the treatment of some diseases and can be used as good adjutants for vaccines. Furthermore, TLR7/8 agonists as potential therapeutics for tumor-targeted immunotherapy have been developed. In this review, we summarize the recent advances in the development of immunotherapy strategies targeting TLR7/8 in patients with various cancers and chronic hepatitis B.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

Fig. 2