Quantitative and functional characteristics of circulating and bone marrow PD-1- and TIM-3-positive T cells in treated multiple myeloma patients

The aim of the present work was to evaluate counts and functional properties of PD-1 and TIM-3 T cells in peripheral blood (PB) and bone marrow (BM) of multiple myeloma (MM) patients following the induction therapy. Sixty patients were enrolled in the study, CD4 and CD8 T cells expressing PD-1 and T...

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Bibliographic Details
Published in:Scientific reports 2020-11, Vol.10 (1), p.20846, Article 20846
Main Authors: Batorov, Egor V, Aristova, Tatiana A, Sergeevicheva, Vera V, Sizikova, Svetlana A, Ushakova, Galina Y, Pronkina, Natalia V, Shishkova, Irina V, Shevela, Ekaterina Y, Ostanin, Alexander A, Chernykh, Elena R
Format: Article
Language:English
Subjects:
Adult
Bone marrow
Bone Marrow - immunology
CD4 antigen
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cytokines
Cytotoxicity
Female
Granzyme B
Granzymes - analysis
Granzymes - metabolism
Humans
Immunophenotyping - methods
Induction therapy
Interferon-gamma - analysis
Interferon-gamma - metabolism
Intracellular
Lymphocytes
Lymphocytes T
Male
Middle Aged
Multiple myeloma
Multiple Myeloma - genetics
Multiple Myeloma - immunology
PD-1 protein
Peripheral blood
Programmed Cell Death 1 Receptor - immunology
Programmed Cell Death 1 Receptor - metabolism
Remission
T-Lymphocyte Subsets - immunology
β2 Microglobulin
γ-Interferon
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Summary:The aim of the present work was to evaluate counts and functional properties of PD-1 and TIM-3 T cells in peripheral blood (PB) and bone marrow (BM) of multiple myeloma (MM) patients following the induction therapy. Sixty patients were enrolled in the study, CD4 and CD8 T cells expressing PD-1 and TIM-3, intracellular production of IFNγ and intracellular expression of Granzyme B were assessed. Relative counts of the majority of circulating PD-1 , TIM-3 and PD-1 TIM-3 T cells were higher in MM patients with disease progression compared with individuals in remission. Frequencies of almost all evaluated PD-1 and TIM-3 T cell subsets were higher in BM samples compared with PB; circulating CD4 PD-1 , CD8 PD-1 , CD8 TIM-3 , CD8 PD-1 TIM-3 T cells positively correlated with the same BM subsets. Circulating CD4 T cells, expressing PD-1 and TIM-3 (including co-expressing subset), as well as CD8 PD-1 TIM-3 T cells, and BM CD8 PD-1 T cells correlated with serum B2-M levels. Sufficient frequencies of GrB and IFNγ subsets in PD-1-expressing T cells indicated their retained functional properties. TIM-3-expressing T cells and double positive PD-1 TIM-3 populations showed diminished cytotoxic and cytokine-producing ability and therefore might be attributed to the exhausted compartment. To identify T cell exhaustion, it is necessary to evaluate T cells co-expressing PD-1, TIM-3 and other inhibitory signal molecules and to study their functional properties. Sustained functionality of PD-1-positive T cells may explain low efficacy and frequent immune-mediated adverse events during anti-PD-1 therapy in MM.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-77941-y