@article {1527654,
	title = {PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity},
	journal = {Nature Immunology},
	volume = {20},
	number = {10},
	year = {2019},
	pages = {1335-1347},
	abstract = {
	CD8+\&nbsp;T cell exhaustion is a state of dysfunction acquired in chronic viral infection and cancer, characterized by the formation of Slamf6+\&nbsp;progenitor exhausted and Tim-3+\&nbsp;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\&nbsp;Ptpn2\&nbsp;in CD8+\&nbsp;T cells increased the generation, proliferative capacity and cytotoxicity of Tim-3+\&nbsp;cells without altering Slamf6+\&nbsp;numbers during lymphocytic choriomeningitis virus clone 13 infection. Likewise, Ptpn2\&nbsp;deletion in CD8+\&nbsp;T cells enhanced Tim-3+\&nbsp;anti-tumor responses and improved tumor control. Deletion of\&nbsp;Ptpn2\&nbsp;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+\&nbsp;T cells can promote effective anti-tumor immunity and implicate PTPN2 in immune cells as an attractive cancer immunotherapy target.



	PubMed\&nbsp;DOI

},
	author = {LaFleur, MW and Nguyen, TH and Coxe, MA and Miller, BC and Yates, KB and Gaudiano, EF and Sen, DR and Gillis, JE and Al Abosy, R and Freeman, G. J. and Haining, WN and Sharpe, A. H.}
}
