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Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
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Antitumor T-cell function requires CPEB4-mediated adaptation to chronic endoplasmic reticulum stress
Marcos Fernández-Alfara1, Annarita Sibilio1, Judit Martin1
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
The EMBO Journal
|March 15, 2023
Summary
Tumor microenvironment stress impairs CD8 T cells. A new pathway involving CPEB4 allows these cells to adapt to chronic endoplasmic reticulum stress, maintaining their anti-tumor function.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Tumor microenvironment (TME) conditions induce endoplasmic reticulum (ER) stress.
- Chronic ER stress impairs CD8 T lymphocyte antitumor function.
- The mechanism for cellular adaptation to sustained ER stress in the TME is unknown.
Purpose of the Study:
- To investigate how CD8 T lymphocytes adapt to chronic ER stress in the TME.
- To identify novel pathways involved in maintaining T cell effector function under stress.
Main Methods:
- Analysis of CD8 T cell responses in the TME.
- Investigated the role of RNA-binding protein CPEB4 in ER stress adaptation.
- Studied the unfolded protein response (UPR) pathway in effector T cells.
Main Results:
- CPEB4 acts as a new branch of the UPR, enabling adaptation to sustained ER stress.
- CPEB4 expression is induced by ER stress during CD8 T cell activation and effector function.
- This CPEB4-mediated UPR branch maintains CD8 T cell fitness, effector molecule production, and cytotoxic activity.
Conclusions:
- CPEB4 is crucial for CD8 T lymphocyte antitumor effector function by mediating adaptation to chronic ER stress.
- Disruption of this CPEB4-dependent pathway exacerbates tumor growth.
- CPEB4 represents a potential therapeutic target for enhancing anti-tumor immunity.
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