ArticleThe Journal of clinical investigation2018
PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Exploring PIM1 Kinase as a Therapeutic Target: Mechanisms and Strategies in Cancer Treatment.International journal of molecular sciences · 2026Review
- Targeting PIM2 improves antitumor immunity through promoting effector function and persistence of CD8 T cells.The Journal of clinical investigation · 2026Article
- Metabolic reprogramming through PIM3 inhibition reverses hypoxia-induced CAR-T cell dysfunction in solid tumors.Journal of translational medicine · 2025Article
- Inhibition of PIM Kinase in Tumor-Associated Macrophages Suppresses Inflammasome Activation and Sensitizes Prostate Cancer to Immunotherapy.Cancer immunology research · 2025Article
- The role of Pim-1 kinases in inflammatory signaling pathways.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma.Signal transduction and targeted therapy · 2024Article
- PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy.Current topics in medicinal chemistry · 2024Review
- PIM kinases regulate early human Th17 cell differentiation.Cell reports · 2023Article
- Time-resolved assessment of single-cell protein secretion by sequencing.Nature methods · 2023Article
- An overview of pim kinase as a target in multiple myeloma.Cancer medicine · 2023Review
- Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.Cell & bioscience · 2023Article
- An XBP1s-PIM-2 positive feedback loop controls IL-15-mediated survival of natural killer cells.Science immunology · 2023Article
- Review
- Pim1 promotes IFN-β production by interacting with IRF3.Experimental & molecular medicine · 2022Article
- PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma.Cancer research · 2022Article
- Feedback Loop Regulation between Pim Kinases and Tax Keeps Human T-Cell Leukemia Virus Type 1 Viral Replication in Check.Journal of virology · 2022Article
- Aberrant metabolic processes promote the immunosuppressive microenvironment in multiple myeloma.Frontiers in immunology · 2022Article
- PIM Kinases in Multiple Myeloma.Cancers · 2021Review
- Novel Pan-Pim Kinase Inhibitors With Imidazopyridazine and Thiazolidinedione Structure Exert Potent Antitumor Activities.Frontiers in pharmacology · 2021Article
- Anti-Inflammatory Effects of the Novel PIM Kinase Inhibitor KMU-470 in RAW 264.7 Cells through the TLR4-NF-κB-NLRP3 Pathway.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
PIM 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.