Tonic signaling in CAR-T therapy: the lever long enough to move the planet

doi:10.1007/s11684-025-1130-x

	Tonic signaling in CAR-T therapy: the lever long enough to move the planet
	Huang, Yuwei1,2 ; Wang, Haopeng1,3,4
	2025-03-01
发表期刊	FRONTIERS OF MEDICINE (IF:3.9[JCR-2023],5.4[5-Year])
ISSN	2095-0217
EISSN	2095-0225
发表状态	已发表
DOI	10.1007/s11684-025-1130-x
摘要	Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in treating hematological malignancies and is expanding into other indications such as autoimmune diseases, fibrosis, aging and viral infection. However, clinical challenges persist in treating solid tumors, including physical barriers, tumor heterogeneity, poor in vivo persistence, and T-cell exhaustion, all of which hinder therapeutic efficacy. This review focuses on the critical role of tonic signaling in CAR-T therapy. Tonic signaling is a low-level constitutive signaling occurring in both natural and engineered antigen receptors without antigen stimulation. It plays a pivotal role in regulating immune cell homeostasis, exhaustion, persistence, and effector functions. The "Peak Theory" suggests an optimal level of tonic signaling for CAR-T function: while weak tonic signaling may result in poor proliferation and persistence, excessively strong signaling can cause T cell exhaustion. This review also summarizes the recent progress in mechanisms underlying the tonic signaling and strategies to fine-tune the CAR tonic signaling. By understanding and precisely modulating tonic signaling, the efficacy of CAR-T therapies can be further optimized, offering new avenues for treatment across a broader spectrum of diseases. These findings have implications beyond CAR-T cells, potentially impacting other engineered immune cell therapies such as CAR-NK and CAR-M.
关键词	CAR-T tonic signal CAR signaling antigen receptor CAR-NK CAR-macrophage
URL	查看原文
收录类别	SCI
语种	英语
资助项目	Science Fund Original Exploratory Program[82350110] ; National Key R&D Program of China[2019YFA0111000] ; Central Guidance on Local Science and Technology Development Fund[YDZX20233100001002] ; Shanghai Local College Capacity Building Project[22010502700]
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS类目	Oncology ; Medicine, Research & Experimental
WOS记录号	WOS:001449447300001
出版者	SPRINGER
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/507042
专题	生命科学与技术学院生命科学与技术学院_PI研究组_王皞鹏组生命科学与技术学院_博士生
通讯作者	Wang, Haopeng
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Lingang Lab, Shanghai 200031, Peoples R China 3.Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China 4.ShanghaiTech Univ, State Key Lab Adv Med Mat & Devices, Shanghai 201210, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院; 上海科技大学
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Huang, Yuwei,Wang, Haopeng. Tonic signaling in CAR-T therapy: the lever long enough to move the planet[J]. FRONTIERS OF MEDICINE,2025.
APA	Huang, Yuwei,&Wang, Haopeng.(2025).Tonic signaling in CAR-T therapy: the lever long enough to move the planet.FRONTIERS OF MEDICINE.
MLA	Huang, Yuwei,et al."Tonic signaling in CAR-T therapy: the lever long enough to move the planet".FRONTIERS OF MEDICINE (2025).