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PTPN2 regulates the generation of exhausted CD8 T cell subpopulations and restrains tumor immunity.

著者 LaFleur MW , Nguyen TH , Coxe MA , Miller BC , Yates KB , Gillis JE , Sen DR , Gaudiano EF , Al Abosy R , Freeman GJ , Haining WN , Sharpe AH
Nat Immunol.2019 Sep 16 ; ():.
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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-3CD8 T cells can promote effective anti-tumor immunity and implicate PTPN2 in immune cells as an attractive cancer immunotherapy target.
PMID: 31527834 [PubMed - as supplied by publisher]
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