| First Author | Dejaegher J | Year | 2017 |
| Journal | Int J Cancer | Volume | 141 |
| Issue | 9 | Pages | 1891-1900 |
| PubMed ID | 28681455 | Mgi Jnum | J:247848 |
| Mgi Id | MGI:5927281 | Doi | 10.1002/ijc.30877 |
| Citation | Dejaegher J, et al. (2017) Characterization of PD-1 upregulation on tumor-infiltrating lymphocytes in human and murine gliomas and preclinical therapeutic blockade. Int J Cancer 141(9):1891-1900 |
| abstractText | Blockade of the immune checkpoint molecule programmed-cell-death-protein-1 (PD-1) yielded promising results in several cancers. To understand the therapeutic potential in human gliomas, quantitative data describing the expression of PD-1 are essential. Moreover, due the immune-specialized region of the brain in which gliomas arise, differences between tumor-infiltrating and circulating lymphocytes should be acknowledged. In this study we have used flow cytometry to quantify PD-1 expression on tumor-infiltrating T cells of 25 freshly resected glioma cell suspensions (10 newly and 5 relapsed glioblastoma, 10 lower grade gliomas) and simultaneously isolated circulating T cells. A strong upregulation of PD-1 expression in the tumor microenvironment compared to the blood circulation was seen in all glioma patients. Additionally, circulating T cells were isolated from 15 age-matched healthy volunteers, but no differences in PD-1 expression were found compared to glioma patients. In the murine GL261 malignant glioma model, there was a similar upregulation of PD-1 on brain-infiltrating lymphocytes. Using a monoclonal PD-1 blocking antibody, we found a marked prolonged survival with 55% of mice reaching long-term survival. Analysis of brain-infiltrating cells 21 days after GL261 tumor implantation showed a shift in infiltrating lymphocyte subgroups with increased CD8+ T cells and decreased regulatory T cells. Together, our results suggest an important role of PD-1 in glioma-induced immune escape, and provide translational evidence for the use of PD-1 blocking antibodies in human malignant gliomas. |
