Scientific publications
Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance
Cirino Botta # 1 2 , Cristina Perez # 3 , Marta Larrayoz 3 , Noemi Puig 4 , Maria-Teresa Cedena 5 , Rosalinda Termini 3 , Ibai Goicoechea 3 , Sara Rodriguez 3 , Aintzane Zabaleta 3 , Aitziber Lopez 3 , Sarai Sarvide 3 , Laura Blanco 3 , Daniele M Papetti 6 , Marco S Nobile 7 8 , Daniela Besozzi 6 8 , Massimo Gentile 9 , Pierpaolo Correale 10 , Sergio Siragusa 11 , Albert Oriol 12 , Maria Esther González-Garcia 13 , Anna Sureda 14 , Felipe de Arriba 15 , Rafael Rios Tamayo 16 , Jose-Maria Moraleda 15 , Mercedes Gironella 17 , Miguel T Hernandez 18 , Joan Bargay 19 , Luis Palomera 20 , Albert Pérez-Montaña 21 , Hartmut Goldschmidt 22 , Hervé Avet-Loiseau 23 , Aldo Roccaro 24 , Alberto Orfao 25 26 , Joaquin Martinez-Lopez 5 , Laura Rosiñol 27 , Juan-José Lahuerta 5 , Joan Blade 27 , Maria-Victoria Mateos 4 , Jesús F San-Miguel 3 , Jose-Angel Martinez Climent 3 , Bruno Paiva 28 ; Programa Para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) cooperative group; iMMunocell study group
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.
CITATION Nat Commun. 2023 Sep 20;14(1):5825. doi: 10.1038/s41467-023-41562-6
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