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dc.contributor.authorDaenthanasanmak, Anusara
dc.contributor.authorWu, Yongxia
dc.contributor.authorIamsawat, Supinya
dc.contributor.authorNguyen, Hung D.
dc.contributor.authorBastian, David
dc.contributor.authorZhang, MengMeng
dc.contributor.authorSofi, M. Hanief
dc.contributor.authorChatterjee, Shilpak
dc.contributor.authorHill, Elizabeth G.
dc.contributor.authorMehrotra, Shikhar
dc.contributor.authorKraft, Andrew S.
dc.contributor.authorYu, Xue-Zhong
dc.date.accessioned2018-09-04T20:02:40Z
dc.date.available2018-09-04T20:02:40Z
dc.date.issued2018-07-02
dc.identifier.citationJ Clin Invest. 2018;128(7):2787-2801. https://doi.org/10.1172/JCI95407.en_US
dc.identifier.issn0021-9738
dc.identifier.issn1558-8238
dc.identifier.pmid29781812
dc.identifier.doi10.1172/JCI95407
dc.identifier.doi10.1172/JCI95407DS1
dc.identifier.urihttp://hdl.handle.net/10150/628648
dc.description.abstractPIM kinase family members play a crucial role in promoting cell survival and proliferation via phosphorylation of their target substrates. In this study, we investigated the role of the PIM kinases with respect to T cell responses in transplantation and tumor immunity. We found that the PIM-2 isoform negatively regulated T cell responses to alloantigen, in contrast to the PIM-1 and PIM-3 isoforms, which acted as positive regulators. T cells deficient in PIM-2 demonstrated increased T cell differentiation toward Th1 subset, proliferation, and migration to target organs after allogeneic bone marrow transplantation, resulting in dramatically accelerated graft-versus-host disease (GVHD) severity. Restoration of PIM-2 expression markedly attenuated the pathogenicity of PIM-2-deficient T cells to induce GVHD. On the other hand, mice deficient in PIM-2 readily rejected syngeneic tumor, which was primarily dependent on CD8(+) T cells. Furthermore, silencing PIM-2 in polyclonal or antigen-specific CD8(+) T cells substantially enhanced their antitumor response in adoptive T cell immunotherapy. We conclude that PIM-2 kinase plays a prominent role in suppressing T cell responses, and provide a strong rationale to target PIM-2 for cancer immunotherapy.en_US
dc.description.sponsorshipBiostatistics Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]; University of Arizona Cancer Center [P30 CA023074]; NIH [R01CA173200, R01 CA169116, R01 AI118305, R01 HL137373, R21 CA192202]; DOD [W81XWH-12-1-0560]; SmartState Endowment in Cancer Stem Cell Biology & Therapy Programen_US
dc.language.isoenen_US
dc.publisherAMER SOC CLINICAL INVESTIGATION INCen_US
dc.relation.urlhttps://www.jci.org/articles/view/95407en_US
dc.relation.urlhttp://www.jci.org/articles/view/95407/sd/1en_US
dc.rightsCopyright © 2018, American Society for Clinical Investigation.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.titlePIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunityen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Ctr Cancen_US
dc.identifier.journalJOURNAL OF CLINICAL INVESTIGATIONen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleJournal of Clinical Investigation
dc.source.volume128
dc.source.issue7
dc.source.beginpage2787
dc.source.endpage2801
refterms.dateFOA2018-09-04T20:02:41Z


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