The immune system relies on T cells to defend against infections and cancer, but it also needs to control their activity to prevent harmful autoimmune reactions. Recent research has shown that natural killer (NK) cells play a role in regulating T cell activity by killing activated T cells to limit their proliferation. A protein called B7H6 was identified as a recognition molecule that marks activated T cells as targets for NK cell attacks. By destroying the B7H6 gene in T cells, researchers were able to protect them from NK cell-induced cell lysis, revealing a mechanism by which the immune system controls the activity of T cells to prevent destructive immune responses.
NK cells can also impact cancer therapies that target immune checkpoint molecules, such as immune checkpoint inhibitors (ICI). The presence of NK cells in tumor tissues of patients receiving ICI therapy was associated with poorer treatment response and shorter progression-free survival. These findings suggest that the B7H6-mediated elimination of tumor-reactive T cells by NK cells could counteract the effectiveness of ICI cancer immunotherapy. This emphasizes the need to understand the role of NK cells in modulating immune responses in the context of cancer therapy.
Cellular immunotherapies, such as CAR-T cell therapy, have shown promise in treating certain cancers by equipping T cells with customized receptors to target cancer cells. However, the effectiveness of these therapies can be limited by the rapid decline in therapeutic T cell numbers post-treatment. It was found that therapeutic CAR-T cells expressing B7H6 on their surface were susceptible to elimination by NK cells, leading to a decrease in therapeutic cell numbers and an increase in tumor load in a mouse model. This highlights the potential impact of NK cell control on various forms of cancer immunotherapy and the importance of developing strategies to protect therapeutic T cells from NK cell-mediated elimination.
Interventions targeting the interaction between NK and T cells could potentially enhance the efficacy of cellular immunotherapies in cancer treatment. By using CRISPR-Cas gene editing technology, researchers aim to protect CAR-T cells from NK cell-induced elimination in a clinical trial. This innovative approach aims to improve the effectiveness of cellular immunotherapy by modulating the immune response to enhance the survival and function of therapeutic T cells. The findings from this study shed light on a previously unknown mechanism by which the immune system regulates T cell activity and its implications for cancer therapy.
