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

Anusara Daenthanasanmak, Yongxia Wu, Supinya Iamsawat, Hung D. Nguyen, David Bastian, Meng Meng Zhang, M. Hanief Sofi, Shilpak Chatterjee, Elizabeth G. Hill, Shikhar Mehrotra, Andrew S. Kraft, Xue Zhong Yu

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2787-2801
Number of pages15
JournalJournal of Clinical Investigation
Volume128
Issue number7
DOIs
StatePublished - Jul 2 2018

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Protein Kinases
Immunity
Transplantation
T-Lymphocytes
Neoplasms
Phosphotransferases
Graft vs Host Disease
Immunotherapy
Protein Isoforms
CD8 Antigens
Isoantigens
Homologous Transplantation
Bone Marrow Transplantation
Virulence
Cell Differentiation
Cell Survival
Phosphorylation
Cell Proliferation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Daenthanasanmak, A., Wu, Y., Iamsawat, S., Nguyen, H. D., Bastian, D., Zhang, M. M., ... Yu, X. Z. (2018). PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity. Journal of Clinical Investigation, 128(7), 2787-2801. https://doi.org/10.1172/JCI95407

PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity. / Daenthanasanmak, Anusara; Wu, Yongxia; Iamsawat, Supinya; Nguyen, Hung D.; Bastian, David; Zhang, Meng Meng; Sofi, M. Hanief; Chatterjee, Shilpak; Hill, Elizabeth G.; Mehrotra, Shikhar; Kraft, Andrew S.; Yu, Xue Zhong.

In: Journal of Clinical Investigation, Vol. 128, No. 7, 02.07.2018, p. 2787-2801.

Research output: Contribution to journalArticle

Daenthanasanmak, A, Wu, Y, Iamsawat, S, Nguyen, HD, Bastian, D, Zhang, MM, Sofi, MH, Chatterjee, S, Hill, EG, Mehrotra, S, Kraft, AS & Yu, XZ 2018, 'PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity', Journal of Clinical Investigation, vol. 128, no. 7, pp. 2787-2801. https://doi.org/10.1172/JCI95407
Daenthanasanmak A, Wu Y, Iamsawat S, Nguyen HD, Bastian D, Zhang MM et al. PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity. Journal of Clinical Investigation. 2018 Jul 2;128(7):2787-2801. https://doi.org/10.1172/JCI95407
Daenthanasanmak, Anusara ; Wu, Yongxia ; Iamsawat, Supinya ; Nguyen, Hung D. ; Bastian, David ; Zhang, Meng Meng ; Sofi, M. Hanief ; Chatterjee, Shilpak ; Hill, Elizabeth G. ; Mehrotra, Shikhar ; Kraft, Andrew S. ; Yu, Xue Zhong. / PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity. In: Journal of Clinical Investigation. 2018 ; Vol. 128, No. 7. pp. 2787-2801.
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