Scientific publications

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

Sep 20, 2023 | Magazine: Nature Communications

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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Director | Principal Investigator Cytometry Platform
Dr. Marta Larráyoz Ilundáin