PD-1^(+)and TIM-3^(+)T cells widely express commonγ-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  

作　　者：EGOR V.BATOROV ALISA D.INESHINA TATIANA A.ARISTOVA VERA V.DENISOVA SVETLANA A.SIZIKOVA DARIA S.BATOROVA GALINA Y.USHAKOVA EKATERINA Y.SHEVELA ELENA R.CHERNYKH 

机构地区：[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

出　　处：《Oncology Research》2024年第10期1575-1587,共13页肿瘤学研究（英文）

基　　金：the Russian Science Foundation(Grant No.20-75-10132).

摘　　要：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 commonγ-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 upregulating PD-1 and TIM-3 checkpoint molecules.Methods:The expression of CD25,CD122,CD127 commonγ-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 commonγ-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 commonγ-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 commonγ-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

关 键 词：Autologous hematopoietic stem cell transplantation(AHSCT) CD25 CD122 Eomesodermin(EOMES) Homeostatic proliferation 

分 类 号：R733.3[医药卫生—肿瘤]