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http://hdl.handle.net/2445/209227
Title: | Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance |
Author: | Botta, Cirino Pérez, Cristina Larrayoz, Marta Puig, Noemí Cedena, María Teresa Termini, Rosalinda Goicoechea, Ibai Rodríguez, Sara Zabaleta, Aintzane Lopez, Aitziber Sarvide, Sarai Blanco, Laura Papetti, Daniele M. Nobile, Marco S. Besozzi, Daniela Gentile, Massimo Correale, Pierpaolo Siragusa, Sergio Oriol, Albert González García, Maria Esther Sureda, Anna Arriba, Felipe de Rios 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 Martínez López, Joaquín Rosiñol, Laura Lahuerta, Juan José Blade, Joan Mateos, María Victoria San Miguel, Jesús F. Martínez Climent, José Ángel Paiva, Bruno Programa Para El Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) Cooperative Group Immunocell Study Group |
Keywords: | Mieloma múltiple Resistència als medicaments Multiple Myeloma Drug resistance |
Issue Date: | 20-Sep-2023 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | 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. Myelomagenesis progresses through well-defined pre-malignant states. Here, using single-cell RNA sequencing and T cell receptor repertoire analysis of bone marrow T cells in patients at different stages of myelomagenesis, the authors identify large clonotypic expansions characterized by the expression of multiple immune checkpoints. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-023-41562-6 |
It is part of: | Nature Communications, 2023, vol. 14, num. 1 |
URI: | http://hdl.handle.net/2445/209227 |
Related resource: | https://doi.org/10.1038/s41467-023-41562-6 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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s41467-023-41562-6.pdf | 3.83 MB | Adobe PDF | View/Open |
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