2026-04-17T18:51:14Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc Botta, Cirino author Perez, Cristina author Larrayoz, Marta author Puig, Noemí author Cedena, María Teresa author Termini, Rosalinda author Goicoechea, Ibai author Rodriguez, Sara author Zabaleta, Aintzane author Lopez, Aitziber author Sarvide, Sarai author Blanco Fernández, Laura author Papetti, Daniele Marco author Nobile, M.S. author Besozzi, Daniela author Gentile, Massimo author Correale, Pierpaolo author Siragusa, Sergio author Oriol, Albert author González Garcia, Maria Esther author Sureda, Anna author De Arriba, Felipe author Ríos-Tamayo, Rafael author Moraleda, José María author Gironella, Mercedes author Hernández, Miguel T. author Bargay, Joan author Palomera, Luís author Pérez-Montaña, Albert author Goldschmidt, Hartmut author Avet-Loiseau, Hervé author Roccaro, Aldo author Orfao, Alberto author Martinez-Lopez, Joaquín author Rosiñol, Laura author Lahuerta, J. J author Bladé Creixenti, Juan author Mateos, M. V author San-Miguel, J author Martinez Climent, Juan-José author Paiva, Bruno author 2023 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. Adult Animals Clone Cells Humans Lenalidomide Mice Multiple Myeloma Programmed Cell Death 1 Receptor T-Lymphocytes Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance