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Updated: Jul 6, 2025
07:55
Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
Published on: January 17, 2025
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Transgelin 2 guards T cell lipid metabolic programming and anti-tumor function
Sung-Min Hwang1,2, Deepika Awasthi1,2, Jieun Jeong3
1Department of Obstetrics and Gynecology, Weill Cornell Medicine. New York, NY 10065, USA.
Research Square
|January 3, 2024
Summary
Transgelin 2 (TAGLN2) is crucial for CD8+ T cell metabolism and anti-cancer immunity by regulating fatty acid uptake. Restoring TAGLN2 in T cells can overcome tumor-induced dysfunction and enhance cancer immunotherapy.
Area of Science:
- Immunology
- Cellular Metabolism
- Cancer Biology
Background:
- Effective immunity against tumors requires T cells to be metabolically programmed by extracellular fatty acids.
- Fatty-acid-binding protein 5 (FABP5) imports lipids, fueling T cell respiration and energy needs.
- The precise mechanisms controlling this immunometabolic pathway are not well understood.
Approach:
- Investigated the role of cytoskeletal organizer Transgelin 2 (TAGLN2) in CD8+ T cell function.
- Examined the interaction between TAGLN2 and FABP5 in lipid uptake and mitochondrial respiration.
- Analyzed TAGLN2 expression in ovarian cancer T cells and its response to tumor microenvironment stress.
Key Points:
- TAGLN2 is essential for CD8+ T cell fatty acid uptake, mitochondrial respiration, and anti-cancer activity.
- TAGLN2 interacts with FABP5, facilitating FABP5's surface localization on activated T cells.
- Tumor-induced endoplasmic reticulum (ER) stress suppresses TAGLN2 in tumor-infiltrating CD8+ T cells, leading to dysfunction.
Conclusions:
- Restoring TAGLN2 in ER-stressed T cells enhances their metabolic function and cytotoxic capacity.
- Overexpressing TAGLN2 in CAR T cells improves therapeutic efficacy in metastatic ovarian cancer models.
- TAGLN2's role in T cell lipid metabolism offers a potential target for enhancing cellular immunotherapy in solid tumors.
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