PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity

The Journal of Clinical Investigation
Anusara DaenthanasanmakXue-Zhong Yu

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 immuno...Continue Reading

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Citations

Dec 29, 2019·Cancer Research·Johannes C MelmsBenjamin Izar
Oct 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shilpak ChatterjeeShikhar Mehrotra
Dec 12, 2020·Molecular Cancer Therapeutics·Rachel K Toth, Noel A Warfel

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Methods Mentioned

BETA
X-Ray
flow cytometry
density gradient centrifugation
PMA
PCR

Software Mentioned

GraphPad Prism

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