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oai:recercat.cat:2072/4743202025-10-05T12:25:10Zcom_2072_98col_2072_378192

urn:hdl:2072/474320 Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance Botta, Cirino Perez, Cristina Larrayoz, Marta Puig, Noemí Cedena, María Teresa Termini, Rosalinda Goicoechea, Ibai Rodriguez, Sara Zabaleta, Aintzane Lopez, Aitziber Sarvide, Sarai Blanco Fernández, Laura Papetti, Daniele Marco Nobile, M.S. Besozzi, Daniela Gentile, Massimo Correale, Pierpaolo Siragusa, Sergio Oriol, Albert González Garcia, Maria Esther Sureda, Anna De Arriba, Felipe Ríos-Tamayo, Rafael Moraleda, José María Gironella, Mercedes Hernández, Miguel T. Bargay, Joan Palomera, Luís Pérez-Montaña, Albert Goldschmidt, Hartmut Avet-Loiseau, Hervé Roccaro, Aldo Orfao, Alberto Martinez-Lopez, Joaquín Rosiñol, Laura Lahuerta, J. J Bladé Creixenti, Juan Mateos, M. V San-Miguel, J Martinez Climent, Juan-José Paiva, Bruno Adult Animals Clone Cells Humans Lenalidomide Mice Multiple Myeloma Programmed Cell Death 1 Receptor T-Lymphocytes Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27 and CD27 T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations. 2023 Article European Commission 680200 Instituto de Salud Carlos III AC17/00101 Ministerio de Economía y Competitividad CB16/12/00369 Instituto de Salud Carlos III PI17/01243 Instituto de Salud Carlos III PI19/00818 Instituto de Salud Carlos III PI20/00048 Nature communications ; Vol. 14 Núm. 1 (december 2023), p. 5825 open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/