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PD-1+ and TIM-3+ T cells widely express common γ-chain cytokine receptors in multiple myeloma patients, and IL-2, IL-7, IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells

EGOR V. BATOROV1,2,*, ALISA D. INESHINA2, TATIANA A. ARISTOVA3, VERA V. DENISOVA3, SVETLANA A. SIZIKOVA3, DARIA S. BATOROVA3, GALINA Y. USHAKOVA3, EKATERINA Y. SHEVELA1, ELENA R. CHERNYKH1

1 Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, 630099, Russia
2 V. Zelman Institute of Medicine and Psychology, Novosibirsk National Research State University, Novosibirsk, 630090, Russia
3 Department of Hematology and Bone Marrow Transplantation, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, 630099, Russia

* Corresponding Author: EGOR V. BATOROV. Email: email

Oncology Research 2024, 32(10), 1575-1587. https://doi.org/10.32604/or.2024.047893

Abstract

Background: Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma (MM) progression. Simultaneously, previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with common γ-chain family cytokines in vitro and during homeostatic proliferation. The aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets up-regulating PD-1 and TIM-3 checkpoint molecules. Methods: The expression of CD25, CD122, CD127 common γ-chain cytokine receptors, phosphorylated signal transducer and activator of transcription-5 (pSTAT5) and eomesodermin (EOMES) was comparatively assessed with flow cytometry in PD-1- and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM patients. Results: Substantial proportions of PD-1- and TIM-3-positive T lymphocytes expressed common γ-chain cytokine receptors and pSTAT5. Frequencies of cytokine receptor expressing cells were significantly higher within TIM-3+ T cells compared to PD-1+TIM-3 subsets. Considerable proportions of both PD-1-/TIM-3-negative and positive CD8+ T cells express EOMES, while only moderate frequencies of CD4+ PD-1+/TIM-3+ T cells up-regulate this transcription factor. Besides, the surface presence of CD25 and intranuclear expression of EOMES in CD4+ T cells were mutually exclusive regardless of PD-1 and TIM-3 expression. The stimulation with common γ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+ and TIM-3+ T cell subsets in vitro. Conclusions: Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine stimulation. Differences in common γ-chain cytokine receptor expression between PD-1+ and TIM-3+ T cells may reflect functional dissimilarity of these cell subsets. Checkpoint blockade appears to alleviate lymphopenia-induced proliferation of PD-1+ T cells but may raise the possibility of immune-mediated adverse events.

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APA Style
BATOROV, E.V., INESHINA, A.D., ARISTOVA, T.A., DENISOVA, V.V., SIZIKOVA, S.A. et al. (2024). Pd-1+ and tim-3+ T cells widely express common γ-chain cytokine receptors in multiple myeloma patients, and IL-2, IL-7, IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells. Oncology Research, 32(10), 1575-1587. https://doi.org/10.32604/or.2024.047893
Vancouver Style
BATOROV EV, INESHINA AD, ARISTOVA TA, DENISOVA VV, SIZIKOVA SA, BATOROVA DS, et al. Pd-1+ and tim-3+ T cells widely express common γ-chain cytokine receptors in multiple myeloma patients, and IL-2, IL-7, IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells. Oncol Res. 2024;32(10):1575-1587 https://doi.org/10.32604/or.2024.047893
IEEE Style
E.V. BATOROV et al., "PD-1+ and TIM-3+ T cells widely express common γ-chain cytokine receptors in multiple myeloma patients, and IL-2, IL-7, IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells," Oncol. Res., vol. 32, no. 10, pp. 1575-1587. 2024. https://doi.org/10.32604/or.2024.047893



cc Copyright © 2024 The Author(s). Published by Tech Science Press.
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