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s41467-023-41562-6.pdf (3.74 MB)

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2023-09-20

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cc by (c) Botta, Cirino et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/209227

Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance

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https://doi.org/10.1038/s41467-023-41562-6

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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.

Matèries

Mieloma múltiple, Resistència als medicaments

Matèries (anglès)

Multiple Myeloma, Drug resistance

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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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, Luis, PÉREZ MONTAÑA, Albert, GOLDSCHMIDT, Hartmut, AVET LOISEAU, Hervé, ROCCARO, Aldo, ORFAO, Alberto, MARTÍNEZ LÓPEZ, Joaquín, ROSIÑOL DACHS, 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. Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance. _Nature Communications_. 2023. Vol. 14, núm. 1. [consulta: 24 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/209227]

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