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

First Author	Botta C	Year	2023
Journal	Nat Commun	Volume	14
Issue	1	Pages	5825
PubMed ID	37730678	Mgi Jnum	J:340766
Mgi Id	MGI:7530319	Doi	10.1038/s41467-023-41562-6
Citation	Botta C, et al. (2023) Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance. Nat Commun 14(1):5825

abstractText

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.

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

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