Grant: Travel Awards - Institute Community Support

One way for cancer to progress is by avoiding the immune system. Researchers found evidence that when cancer cells are exposed to low oxygen levels, they acquire more aggressive behavior such as metastasis, resistance to therapy and immune destruction. However, the link between exposure to low oxygen and cancer cells escaping immunity is poorly understood. In the past, we showed that low oxygen levels favor the survival of cancer cells that are resistant to killing by immune cells called natural killer (NK) cells. We found that cancer cells exposed to low oxygen release certain surface molecules called MICA that make them vulnerable to killing by NK cells. We also reported that treatment of cancer cells with nitroglycerine, a well-known drug used in treatment of chest pain restored their vulnerability to killing by NK cells. In the current study, we report in details the molecular mechanism by which cancer cells exposed to low oxygen release MICA molecules to avoid killing by NK cells. We also show how nitroglycerine works at the molecular level to suppress the loss of MICA from cancer cells, thus restoring their vulnerability to killing by NK cells. To validate all results in a context closer to the human biology, we adopted a mouse model in which human prostate cancer cells were injected under skin of mice and allowed to form tumors. When tumor-bearing mice were treated with transdermal patches of nitroglycerine, they showed slower tumor growth than the ones treated with placebo patches. This research opens new hopes to fight cancer by using nitroglycerine as a supplemental treatment to block the resistance of cancer cells to the immune system.