David Barras, Eleonora Ghisoni, Johanna Chiffelle, Angela Orcurto, Julien Dagher, Noémie Fahr, Fabrizio Benedetti, Isaac Crespo, Alizée J Grimm, Matteo Morotti, Stefan Zimmermann, Rafael Duran, Martina Imbimbo, Maria Ochoa de Olza, Blanca Navarro, Krisztian Homicsko, Sara Bobisse, Danny Labes, Zoe Tsourti, Charitini Andriakopoulou, Fernanda Herrera, Rémy Pétremand, Reinhard Dummer, Gregoire Berthod, Anne I Kraemer, Florian Huber, Jonathan Thevenet, Michal Bassani-Sternberg, Niklaus Schaefer, John O Prior, Maurice Matter, Veronica Aedo, Clarisse Dromain, Jesus Corria-Osorio, Stéphanie Tissot, Lana E Kandalaft, Raphael Gottardo, Mikaël Pittet, Christine Sempoux, Olivier Michielin, Urania Dafni, Lionel Trueb, Alexandre Harari, Denarda Dangaj Laniti, George Coukos
Adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell-intrinsic immunogenicity and mutational burden...
February 2, 2024: Science Immunology