| First Author | Daenthanasanmak A | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 7 | Pages | 2787-2801 |
| PubMed ID | 29781812 | Mgi Jnum | J:265434 |
| Mgi Id | MGI:6197590 | Doi | 10.1172/JCI95407 |
| Citation | Daenthanasanmak A, et al. (2018) PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity. J Clin Invest 128(7):2787-2801 |
| abstractText | 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. |
