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• W2014189487 abstract "Weak T-cell antigen receptor (TCR)-ligand interactions are sufficient to activate naïve CD8(+) T cells, but generally do not result in tumor eradication. How differences in TCR affinity affect the regulation of T-cell function in an immunosuppressive tumor environment has not been investigated. We have examined the functional differences of high- vs. low-affinity CD8(+) T cells and we observed that infiltration, accumulation, survival and cytotoxicity within the tumor are severely impacted by the strength of TCR-ligand interactions. In addition, high-affinity CD8(+) T cells were found to exhibit lower expression of inhibitory molecules including PD-1, LAG-3 and NKG2A, thus being less susceptible to suppressive mechanisms. Interferon γ and autocrine interleukin-2 were both found to influence the level of expression of these molecules. Interestingly, although high-affinity CD8(+) T cells were superior to low-affinity CD8(+) T cells in their ability to effect tumor eradication, they could be further improved by the presence of tumor specific CD4(+) T cells. These findings illustrate the importance of both TCR affinity and tumor-specific CD4 help in tumor immunotherapy." @default.
• W2014189487 created "2016-06-24" @default.
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• W2014189487 date "2012-11-01" @default.
• W2014189487 modified "2023-09-23" @default.
• W2014189487 title "Functional differences between low- and high-affinity CD8⁺T cells in the tumor environment" @default.
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• W2014189487 doi "https://doi.org/10.4161/onci.21285" @default.
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