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PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity
- Source :
- Nature Immunology. 20:1335-1347
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
T cell
Immunology
Biology
Lymphocytic choriomeningitis
medicine.disease
3. Good health
Immune tolerance
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Immune system
Cancer immunotherapy
medicine
Cancer research
Immunology and Allergy
Cytotoxic T cell
Clone (B-cell biology)
CD8
030215 immunology
Subjects
Details
- ISSN :
- 15292916 and 15292908
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Nature Immunology
- Accession number :
- edsair.doi...........992756eca413d6aee6ab35f18e3ef5b5