| First Author | Jing W | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 20 | Pages | 5676-5686 |
| PubMed ID | 28916658 | Mgi Jnum | J:245576 |
| Mgi Id | MGI:5919408 | Doi | 10.1158/0008-5472.CAN-17-1309 |
| Citation | Jing W, et al. (2017) T Cells Deficient in Diacylglycerol Kinase zeta Are Resistant to PD-1 Inhibition and Help Create Persistent Host Immunity to Leukemia. Cancer Res 77(20):5676-5686 |
| abstractText | Efforts to improve the efficacy of adoptive T-cell therapies and immune checkpoint therapies in myelogenous leukemia are desired. In this study, we evaluated the antileukemia activity of adoptively transferred polyclonal cancer antigen-reactive T cells deficient in the regulator diacylglycerol kinase zeta (DGKzeta) with or without PD-1/PD-L1 blockade. In the C1498 mouse model of myeloid leukemia, we showed that leukemia was eradicated more effectively in DGKzeta-deficient (DGKzeta-/-) mice than wild-type mice. T cells transferred from DGKzeta-deficient mice to wild-type tumor-bearing recipients conferred this benefit. Leukemia clearance was similar to mice treated with anti-PD-L1. Strikingly, we found that the activity of adoptively transferred DGKzeta-/- T cells relied partly on induction of sustainable host T-cell immunity. Transferring DGKzeta-deficient T cells increased the levels of IFNgamma and other cytokines in recipient mice, especially with coadministration of anti-PD-L1. Overall, our results offered evidence that targeting DGKzeta may leverage the efficacy of adoptive T-cell and immune checkpoint therapies in leukemia treatment. Furthermore, they suggest that DGKzeta targeting might decrease risks of antigen escape or resistance to immune checkpoint blockade. Cancer Res; 77(20); 5676-86. (c)2017 AACR. |
