Bao Nguyen Rose Hills
Mechanisms of metabolic adaptations as NK resistance in cancer cells
Despite advancements in NK cell research and immunotherapies, the dynamic interactions between NK cells and tumor evasion still leave much to be studied. One novel immunotherapeutic strategy harnessing the ability of NK cells to detect and attack malignant cells is the combinatorial use of a STING agonist, CDN, and a modified IL-2, H9-MSA. This approach has been shown to activate significant, NK-mediated anti-tumor responses in cancer models resistant to CD8+ T cells. However, despite this success, we have observed that tumors treated with CDN/H9-MSA acquire resistance to NK cells. We hypothesize that the NK-resistant tumor cell lines are due to faster growth/metabolic adaptations or loss of important recognition molecules required for NK-mediated cytotoxicity. Understanding the impact of CDN/H9-MSA’s therapeutic effects on progressed malignant cell lines that have developed resistance to NK cells will allow us to evaluate the efficacy of this immunotherapy in more complex malignant models.
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