| Title: |
Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance |
| Authors: |
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; Bladé, J. (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 |
| Source: |
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2023 |
| Collection: |
Dipòsit Digital de la Universitat de Barcelona |
| Subject Terms: |
Mieloma múltiple; Resistència als medicaments; Multiple Myeloma; Drug resistance |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
15 p.; application/pdf |
| Language: |
English |
| Relation: |
Reproducció del document publicat a: https://doi.org/10.1038/s41467-023-41562-6; Nature Communications, 2023, vol. 14, num. 1; https://doi.org/10.1038/s41467-023-41562-6; https://hdl.handle.net/2445/209227 |
| Availability: |
https://hdl.handle.net/2445/209227 |
| Rights: |
cc by (c) Botta, Cirino et al., 2023 ; http://creativecommons.org/licenses/by/3.0/es/ ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.AA19CAAC |
| Database: |
BASE |