| First Author | LaFleur MW | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 10 | Pages | 1335-1347 |
| PubMed ID | 31527834 | Mgi Jnum | J:292891 |
| Mgi Id | MGI:6436068 | Doi | 10.1038/s41590-019-0480-4 |
| Citation | LaFleur MW, et al. (2019) PTPN2 regulates the generation of exhausted CD8(+) T cell subpopulations and restrains tumor immunity. Nat Immunol 20(10):1335-1347 |
| abstractText | CD8(+) T cell exhaustion is a state of dysfunction acquired in chronic viral infection and cancer, characterized by the formation of Slamf6(+) progenitor exhausted and Tim-3(+) terminally exhausted subpopulations through unknown mechanisms. Here we establish the phosphatase PTPN2 as a new regulator of the differentiation of the terminally exhausted subpopulation that functions by attenuating type 1 interferon signaling. Deletion of Ptpn2 in CD8(+) T cells increased the generation, proliferative capacity and cytotoxicity of Tim-3(+) cells without altering Slamf6(+) numbers during lymphocytic choriomeningitis virus clone 13 infection. Likewise, Ptpn2 deletion in CD8(+) T cells enhanced Tim-3(+) anti-tumor responses and improved tumor control. Deletion of Ptpn2 throughout the immune system resulted in MC38 tumor clearance and improved programmed cell death-1 checkpoint blockade responses to B16 tumors. Our results indicate that increasing the number of cytotoxic Tim-3(+)CD8(+) T cells can promote effective anti-tumor immunity and implicate PTPN2 in immune cells as an attractive cancer immunotherapy target. |
