Research output: Contribution to journal › Article › peer-review
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. / Batorov, Egor V; Ineshina, Alisa D; Aristova, Tatiana A et al.
In: Oncology research, Vol. 32, No. 10, 06.2024, p. 1575-1587.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - 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
AU - Batorov, Egor V
AU - Ineshina, Alisa D
AU - Aristova, Tatiana A
AU - Denisova, Vera V
AU - Sizikova, Svetlana A
AU - Batorova, Daria S
AU - Ushakova, Galina Y
AU - Shevela, Ekaterina Y
AU - Chernykh, Elena R
N1 - This work is supported by the Russian Science Foundation (Grant No. 20-75-10132). © 2024 The Authors.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - Humans
KW - Multiple Myeloma/immunology
KW - Hepatitis A Virus Cellular Receptor 2/metabolism
KW - Programmed Cell Death 1 Receptor/metabolism
KW - Middle Aged
KW - Male
KW - Female
KW - Aged
KW - Interleukin-7/metabolism
KW - Interleukin-15/pharmacology
KW - Up-Regulation
KW - Adult
KW - Receptors, Cytokine/metabolism
KW - T-Lymphocytes/immunology
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85204759554&origin=inward&txGid=86c4cee83ecb17e7372614f8e321dbbe
UR - https://www.mendeley.com/catalogue/abdde6c2-f58f-33d6-b28f-9106ce5ab37a/
U2 - 10.32604/or.2024.047893
DO - 10.32604/or.2024.047893
M3 - Article
C2 - 39308517
VL - 32
SP - 1575
EP - 1587
JO - Oncology research
JF - Oncology research
SN - 0965-0407
IS - 10
ER -
ID: 61161009