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Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions
Yali Song1, Yazhi Mo2, Si Chen2
1Department of Laboratory Medicine Shenzhen University General Hospital Shenzhen China.
Medcomm
|March 2, 2026
Summary
Immune exhaustion, a dysfunction from chronic antigen exposure, drives cancer progression. This review explores the infection-exhaustion-tumor axis and strategies to reverse exhaustion for precision oncology.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Immune exhaustion is sustained lymphocyte dysfunction due to chronic antigenic stimulation.
- It is a hallmark of chronic infection and cancer, actively promoting tumor progression by creating immunosuppressive microenvironments.
- Pathogens can induce immune exhaustion, impairing cytotoxic T cell surveillance and facilitating tumorigenesis.
Purpose of the Study:
- To review the mechanisms and characteristics of immune exhaustion in chronic infection and cancer.
- To propose and analyze the chronic infection-exhaustion-tumor axis.
- To critically appraise current strategies for reversing immune exhaustion and discuss their therapeutic potential.
Main Methods:
- Comprehensive literature review integrating insights from virology and immuno-oncology.
- Analysis of the infection-exhaustion-tumor axis with specific pathogen examples.
- Evaluation of therapeutic strategies for immune exhaustion reversal.
Main Results:
- Immune exhaustion actively drives tumor progression and facilitates tumorigenesis.
- A proposed chronic infection-exhaustion-tumor axis links persistent infections to cancer development.
- Current strategies for reversing immune exhaustion show therapeutic potential but have limitations.
Conclusions:
- Immune exhaustion is a critical factor in both chronic infections and cancer progression.
- Targeting the infection-exhaustion-tumor axis offers a novel therapeutic strategy.
- Further research is needed to optimize treatments for immune exhaustion in diverse clinical contexts.
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