NKG2D defines tumor-reacting effector CD8⁺ T cells within tumor microenvironment

For successful immunotherapy for cancer, it is important to understand the immunological status of tumor antigen-specific CD8⁺ T cells in the tumor microenvironment during tumor progression. In this study, we monitored the behavior of B16OVA-Luc cells in mice immunized with a model tumor antigen ovalbumin (OVA). Using bioluminescence imaging, we identified the time series of OVA-specific CD8⁺ T-cell responses during tumor progression: initial progression, immune control, and the escape phase. As a result of analyzing the status of tumor antigen-specific CD8⁺ cells in those 3 different phases, we found that the expression of NKG2D defines tumor-reacting effector CD8⁺ T cells. NKG2D may control the fate and TOX expression of tumor-reacting CD8⁺ T cells, considering that NKG2D blockade in OVA-vaccinated mice delayed the growth of the B16OVA-Luc2 tumor and increased the presence of tumor-infiltrating OVA-specific CD8⁺ T cells.