학술논문
Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance
Document Type
article
Author
Cirino Botta; Cristina Perez; Marta Larrayoz; Noemi Puig; Maria-Teresa Cedena; Rosalinda Termini; Ibai Goicoechea; Sara Rodriguez; Aintzane Zabaleta; Aitziber Lopez; Sarai Sarvide; Laura Blanco; Daniele M. Papetti; Marco S. Nobile; Daniela Besozzi; Massimo Gentile; Pierpaolo Correale; Sergio Siragusa; Albert Oriol; Maria Esther González-Garcia; Anna Sureda; Felipe de Arriba; Rafael Rios Tamayo; Jose-Maria Moraleda; Mercedes Gironella; Miguel T. Hernandez; Joan Bargay; Luis Palomera; Albert Pérez-Montaña; Hartmut Goldschmidt; Hervé Avet-Loiseau; Aldo Roccaro; Alberto Orfao; Joaquin Martinez-Lopez; Laura Rosiñol; Juan-José Lahuerta; Joan Blade; Maria-Victoria Mateos; Jesús F. San-Miguel; Jose-Angel Martinez Climent; Bruno Paiva; the Programa Para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) cooperative group; the iMMunocell study group
Source
Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
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.