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| Home > Articles > Published articles > Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance |
| Home > Articles > Published articles > Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance |
(Clínica Universidad de Navarra) (Clínica Universidad de Navarra) (Hospital Universitario 12 de Octubre) (Clínica Universidad de Navarra) (Clínica Universidad de Navarra) (Department of Informatics. University of Milano-Bicocca) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut d'Investigació Biomèdica de Bellvitge) (Hospital Universitario Puerta de Hierro Majadahonda (Madrid)) (Instituto Murciano de Investigación Biosanitaria) (Hospital Universitari Vall d'Hebron) (Hospital Universitari Son Llàtzer (Palma de Mallorca, Balears)) (Department of Internal Medicine V. University of Heidelberg) (Department of Hematology. ASST Spedali Civili di Brescia) (Universidad de Salamanca. Departamento de Medicina) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Hospital Universitario 12 de Octubre) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Hospital Universitario de SalamancaBiomedica de Salamanca (IBSAL). Centro de Investigación del Cancer (IBMCC-USAL. CSIC)) (Clínica Universidad de Navarra) (Clínica Universidad de Navarra) (Clínica Universidad de Navarra)
| Date: | 2023 |
| 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. |
| Grants: | 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 |
| Rights: | 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.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Adult ; Animals ; Clone Cells ; Humans ; Lenalidomide ; Mice ; Multiple Myeloma ; Programmed Cell Death 1 Receptor ; T-Lymphocytes |
| Published in: | Nature communications, Vol. 14 Núm. 1 (december 2023) , p. 5825, ISSN 2041-1723 |
