Journal
CANCER LETTERS
Volume 506, Issue -, Pages 55-66Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.02.013
Keywords
T cell exhaustion; Tumor microenvironment factors; Inhibitory receptors; Transcriptional factors; Immunotherapy
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Funding
- National Natural Science Foundation of China [81971466, 81972875]
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT310028]
- Chinese Academy of Medical Sciences [2016I2M-1-005, 2016-I2M-1-005]
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Persistent antigen stimulation in chronic infections and cancer leads to CD8(+) T cell exhaustion, characterized by increased expression of co-inhibitory receptors, loss of effector function, and dysregulated metabolic activity. Understanding the molecular mechanisms and key factors shaping exhaustion features within the tumor microenvironment could improve cancer immunotherapy efficacy targeting exhausted T cells.
The persistent antigen stimulation during chronic infections and cancer results in CD8(+) T cell exhaustion. The exhausted T (Tex) cells within the tumor microenvironment (TME) are characterized by increased expression of multiple co-inhibitory receptors simultaneously, progressive loss of effector function, poor proliferation and self-renewal capacity, and dysregulated metabolic activity. Emerging insights into molecular mechanisms underlying T cell exhaustion have proposed potential approaches to improve the efficacy of cancer immunotherapy via restoring the effector function of Tex cells. In this review, we summarize the fundamental characteristics (e.g., inhibitory receptors and transcriptional factors) regarding Tex cell differentiation and discuss in particular how those exhaustion features are acquired and shaped by key factors within the TME. Additionally, we discuss the progress and limitations of current cancer immunotherapeutic strategies targeting Tex cells in clinical setting.
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