c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models

Article Article scientifique Article c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models eng 2023-11-23 2023-11-23 author Benkhoucha Mahdia Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 561017 Département des neurosciences cliniques (OTONO) author Tran Lan 0000-0003-4270-376X Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 597623 Services communs de la faculté de médecine (SCMU) Ngoc Lan Tran author Senoner Isis Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 781453 Département des neurosciences cliniques (OTONO) author Breville Gautier 0000-0003-0890-1981 Department of Clinical Neurosciences, Division of Neurology, University Hospital of Geneva, 1205 Geneva, Switzerland.,Center for Neuroinflammation and Experimental Therapeutics, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 953988 author Fritah Hajer Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 406165 Département des neurosciences cliniques (OTONO) author Migliorini Denis Brain Tumor and Immune Cell Engineering Laboratory, Department of Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.,Department of Oncology, Unit of Neuro-Oncology, University Hospital of Geneva, 1205 Geneva, Switzerland. 838158 Département de médecine (DEMED) author Dutoit Vallotton Valérie 0000-0002-3469-4237 Brain Tumor and Immune Cell Engineering Laboratory, Department of Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 668630 Département de médecine (DEMED) author Lalive d'Epinay Patrice Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.,Department of Clinical Neurosciences, Division of Neurology, University Hospital of Geneva, 1205 Geneva, Switzerland. 636926 Département des neurosciences cliniques (OTONO) 3123 10.3390/biomedicines11123123 38137344 2227-9059 PMC10740932 https://www.mdpi.com/2227-9059/11/12/3123 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 CTL clones expressing c-Met (c-Met+ ) and compared it to c-Met- CTL clones. Our results indicated that, similar to their murine counterparts, c-Met+ human CTL clones exhibited increased cytolytic activity compared to c-Met- CTL 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 promise for developing strategies to enhance the effectiveness of CTL-based immunotherapies against cancer. CD8+ cytotoxic T lymphocytes CTLs HGF C-Met Spheroids Tumor Dewey 616.8 Dewey 616 Dewey 616.07 Swiss National Science Foundation Functional characterization of c-Met-expressing T cells in experimental immunology 176078 CH Projects Swiss National Science Foundation Study of the HGF/c-Met pathway in lymphoid cells and therapeutic approaches in a model of neuroinflammation and multiple sclerosis 214931 CH Projects 56 Département de médecine 221 137 Département de pathologie et immunologie 21F 61 Département des neurosciences cliniques 226 false 1310 Tumeurs cérébrales 1016 505 Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale 843 Biomedicines 11 12 4a09fc2f-d653-4011-b6a9-a32bf031dd75 Article (Published version) Public c-Met_Cytotoxic_T_Lymphocytes_biom.pdf 2839524 application/pdf CC BY-4.0 a51907eb62ecb9199557c8743f6d01b0a13085bf554557f19672f1200ec374b1 0793ce2d-12a0-4ec5-ae40-fca150351465 Appendix Public biomedicines-2665578-supplementary.pdf 564528 application/pdf a0bece71a8969158efdec6d15af954c318a2fb16095e95cce0719f073245746f openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques

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c-Met+ Cytotoxic T Lymphocytes Exhibit Enhanced Cytotoxicity in Mice and Humans In Vitro Tumor Models	Biomedicines			2023	62	244

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