T cell exhaustion in human cancers.
Biochim Biophys Acta Rev Cancer
; 1879(5): 189162, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39089484
ABSTRACT
T cell exhaustion refers to a progressive state in which T cells become functionally impaired due to sustained antigenic stimulation, which is characterized by increased expression of immune inhibitory receptors, but weakened effector functions, reduced self-renewal capacity, altered epigenetics, transcriptional programme and metabolism. T cell exhaustion is one of the major causes leading to immune escape of cancer, creating an environment that supports tumor development and metastatic spread. In addition, T cell exhaustion plays a pivotal role to the efficacy of current immunotherapies for cancer. This review aims to provide a comprehensive view of roles of T cell exhaustion in cancer development and progression. We summerized the regulatory mechanisms that involved in T cell exhaustion, including transcription factors, epigenetic and metabolic reprogramming events, and various microenvironmental factors such as cytokines, microorganisms, and tumor autocrine substances. The paper also discussed the challenges posed by T cell exhaustion to cancer immunotherapies, including immune checkpoint blockade (ICB) therapies and chimeric antigen receptor T cell (CAR-T) therapy, highlightsing the obstacles encountered in ICB therapies and CAR-T therapies due to T cell exhaustion. Finally, the article provides an overview of current therapeutic options aimed to reversing or alleviating T cell exhaustion in ICB and CAR-T therapies. These therapeutic approaches seek to overcome T cell exhaustion and enhance the effectiveness of immunotherapies in treating tumors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Tumor Microenvironment
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Biochim Biophys Acta Rev Cancer
Year:
2024
Document type:
Article
Country of publication:
Netherlands