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CD8+ T cell dysfunction by TOX intoxication: a protumorigenic event in the tumor microenvironment
Nilesh Kumar Sharma1, Sachin C Sarode2, Gargi S Sarode2
1Cancer & Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India.
Future Oncology (London, England)
|November 30, 2021
Summary
Cellular components shift tumor microenvironments. Thymocyte selection-associated high-mobility group-box protein (TOX) drives CD8+ T cell exhaustion, promoting tumor growth and offering new therapeutic targets.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Cellular components play a critical role in modulating tumor microenvironments from antitumor to protumor states.
- CD8+ T cells, crucial for anti-tumor immunity, can transition from effector and memory phenotypes to an exhausted state within the tumor niche.
- This exhaustion of CD8+ T cells contributes to the development of a protumor microenvironment.
Purpose of the Study:
- To summarize the molecular mechanisms linking CD8+ T cells, TOX, and transcriptional/epigenetic reprogramming in cancer.
- To highlight the role of TOX in regulating T cell exhaustion and its implications in tumor immunity.
- To identify future research directions for novel cancer therapeutics targeting these pathways.
Main Methods:
- Review and synthesis of existing experimental data and literature.
- Analysis of molecular mechanisms governing T cell phenotype and function.
- Exploration of the role of TOX in transcriptional and epigenetic regulation.
Main Results:
- Evidence suggests a shift in CD8+ T cell states towards exhaustion within the tumor microenvironment.
- Thymocyte selection-associated high-mobility group-box protein (TOX) is identified as a key regulator of T cell transcriptional and epigenetic reprogramming.
- TOX plays a significant role in promoting T cell exhaustion, impacting tumor immunity.
Conclusions:
- CD8+ T cell exhaustion, regulated by TOX, is a critical mechanism promoting protumor microenvironments.
- Understanding the interplay between CD8+ T cells, TOX, and epigenetic reprogramming is essential for developing effective cancer therapies.
- Targeting TOX and associated pathways presents a promising avenue for future cancer therapeutic strategies.
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