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c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models
Mahdia Benkhoucha1, Ngoc Lan Tran1, Isis Senoner1
1Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Biomedicines
|December 23, 2023
Summary
Hepatocyte growth factor (HGF) receptor c-Met positive cytotoxic T lymphocytes (CTLs) show enhanced anti-tumor immunity. Targeting the HGF/c-Met pathway may improve CTL-based cancer immunotherapies.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Biology
Background:
- CD8+ cytotoxic T lymphocytes (CTLs) are vital for anti-tumor immunity.
- A subset of CTLs expressing the hepatocyte growth factor (HGF) receptor, c-Met (c-Met+ CTLs), exhibit enhanced cytolytic capacity.
- HGF inhibits c-Met+ CTL function, impacting anti-cancer responses.
Purpose of the Study:
- To investigate the function of c-Met+ CTLs in a 3D tumor model.
- To examine the effect of cell-cell contact on inhibitory checkpoint molecules in c-Met+ CTLs.
- To evaluate the cytolytic capacity of human c-Met+ CTL clones and the role of HGF.
Main Methods:
- Studied c-Met+ CTL function within B16 melanoma spheroids (3D model).
- Assessed expression of inhibitory checkpoint molecules (KLRG1, PD-1, CTLA-4) influenced by cell-cell contact.
- Compared cytolytic activity of human c-Met+ and c-Met- CTL clones in the presence and absence of HGF.
Main Results:
- c-Met+ CTLs demonstrated enhanced cytolytic activity in 3D spheroids.
- Human c-Met+ CTL clones showed higher cytolytic capacity than c-Met- CTL clones.
- HGF negatively regulated the enhanced cytolytic function of c-Met+ CTLs.
Conclusions:
- c-Met+ CTLs possess superior anti-tumor cytotoxic potential.
- The HGF/c-Met pathway modulates CTL-mediated anti-tumor immunity.
- Targeting the HGF/c-Met pathway offers a promising strategy for enhancing CTL-based cancer immunotherapies.
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