Benkhoucha, M.; Tran, N.L.; Senoner, I.; Breville, G.; Fritah, H.; Migliorini, D.; Dutoit, V.; Lalive, P.H. c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models. Biomedicines2023, 11, 3123.
Benkhoucha, M.; Tran, N.L.; Senoner, I.; Breville, G.; Fritah, H.; Migliorini, D.; Dutoit, V.; Lalive, P.H. c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models. Biomedicines 2023, 11, 3123.
Benkhoucha, M.; Tran, N.L.; Senoner, I.; Breville, G.; Fritah, H.; Migliorini, D.; Dutoit, V.; Lalive, P.H. c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models. Biomedicines2023, 11, 3123.
Benkhoucha, M.; Tran, N.L.; Senoner, I.; Breville, G.; Fritah, H.; Migliorini, D.; Dutoit, V.; Lalive, P.H. c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models. Biomedicines 2023, 11, 3123.
Abstract
CD8+ cytotoxic T lymphocytes (CTLs) play a crucial role in anti-tumor immunity. In a previous study, we identified a subset of murine effector CTLs expressing the hepatocyte growth factor (HGF) receptor c-Met (c-Met+ CTLs) that are endowed with enhanced cytolytic capacity. HGF directly inhibited the cytolytic function of c-Met+ CTLs, both in 2D in vitro assays and in vivo, leading to reduced T cell responses against metastatic melanoma. To further investigate the role of c-Met+ CTLs in a three-dimensional (3D) setting, we studied their function within B16 melanoma spheroids and examined the impact of cell-cell contact on the modulation of inhibitory checkpoint molecules expression such as KLRG1, PD-1 and CTLA-4. Additionally, we evaluated the cytolytic capacity of human CTLs clones expressing c-Met (c-Met+) and compared it to c-Met− CTLs clones. Our results indicated that, similar to their murine counterparts, c-Met+ human CTLs clones exhibited increased cytolytic activity compared to c-Met− CTLs clones, and this enhanced function was negatively regulated by the presence of HGF. Taken together, our findings highlight the potential of targeting the HGF/c-Met pathway to modulate CTL-mediated anti-tumor immunity. This research holds promises for developing strategies to enhance the effectiveness of CTL-based immunotherapies against cancer.
Keywords
c-Met; HGF; CTLs; CD8+ cytotoxic T lymphocytes; spheroids; tumor
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
