Functional differences between low- and high-affinity CD8+ T cells in the tumor environment

• Published in: Oncoimmunology Vol. 1; no. 8; pp. 1239 - 1247
• Main Authors: Bos, Rinke, Marquardt, Kristi L., Cheung, Jocelyn, Sherman, Linda A.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.11.2012; Landes Bioscience
• Subjects: CD4 help; CD8; Research Paper; T cell function; T cells; TCR affinity; tumor environment
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.4161/onci.21285

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.