AI Article Synopsis
- CD8 T cells can become less effective, or "exhausted," during long-lasting infections and cancer, which leads to different types of exhausted cells.
- Scientists have discovered that a protein called PTPN2 helps control how these exhausted T cells develop and function, especially in fighting tumors.
- By removing PTPN2 from these immune cells, they found that T cells became stronger and better at attacking tumors, suggesting that targeting PTPN2 could be a good way to improve cancer treatments.
Article 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-3CD8 T cells can promote effective anti-tumor immunity and implicate PTPN2 in immune cells as an attractive cancer immunotherapy target.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754306 | PMC |
| http://dx.doi.org/10.1038/s41590-019-0480-4 | DOI Listing |
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