Fiche publication
Date publication
juin 2025
Journal
Science advances
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier
Tous les auteurs :
Saillard M, Cenerenti M, Reichenbach P, Guillaume P, Su Z, Hafezi M, Schmidt J, Cesbron J, Genolet R, Queiroz L, Racle J, Villard J, Renella R, Michielin O, Zoete V, Rivals JP, Irving M, Speiser DE, Harari A, Gfeller D, Adotevi O, Ceppi F, Coukos G, Romero P, Jandus C
Lien Pubmed
Résumé
While cancer immunotherapy has primarily focused on CD8 T cells, CD4 T cells are increasingly recognized for their role in antitumor immunity. The allele is found in 50% of Caucasians. In this study, we screened patients with melanoma for tumor-specific CD4 T cells and identified robust New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/ CD4 T cell activity in both peripheral blood and tumor tissue. By analyzing NY-ESO-1/-restricted CD4 T cell clones, we uncovered an unexpectedly high cytotoxicity, strong T helper 1 polarization, and recurrent αβ T cell receptor (TCRαβ) usage across patients and anatomical sites. These responses were also present in other NY-ESO-1-expressing cancers. TCRs from these clones, when transduced into primary CD4 T cells, showed direct antitumor efficacy both in vitro and in vivo. Our findings suggest that these TCRs are promising for adoptive T cell transfer therapy, enabling broader targeting of NY-ESO-1-expressing adult and pediatric cancers in clinical settings.
Mots clés
Humans, CD4-Positive T-Lymphocytes, immunology, Membrane Proteins, immunology, Antigens, Neoplasm, immunology, Animals, Mice, Receptors, Antigen, T-Cell, genetics, Melanoma, immunology, Cell Line, Tumor, Immunotherapy, Adoptive, Receptors, Antigen, T-Cell, alpha-beta, genetics, Neoplasms, therapy, Cell- and Tissue-Based Therapy, methods
Référence
Sci Adv. 2025 06 27;11(26):eadu5754
