Role of the PI3K / AKT / mTOR pathway in the resistance of acute myeloid leukemia to NK-induced apoptosis

Abstract

The immunotherapies comprehend several strategies which aim to use molecules or cells derived from immune system to induce apoptosis of tumor cells. NK cells are the most important components responsible to recognize and eliminate cancer in our body. However, the immune system of leukemia patients is damaged, and different authors demonstrate that leukemia stem cells are resistant to NK attack. Although the still unclear mechanisms, literature has provided evidences supporting the decreased efficiency of NK-based immunotherapy as a consequence of this resistance behavior of the cancers cells. Considering this issue is absolutely unexplored for acute myeloid leukemia (AML), the current project aims to characterize the role of PI3K/Akt/mTOR pathway, one of the most important pro-survival axis in cancer cells, in the resistance of AML cells to NK attack. Briefly, we will investigate the expression of the main surface molecules of leukemia cells related to activation and inhibition of NK cells, with or without PI3K/Akt/mTOR pathway inhibition. We will also investigate the resistance to apoptosis of AML cells in co-culture with NK cells with or without inhibition of the investigated pathway. The results may disclose the importance of pharmacological inhibition of PI3K/Akt/mTOR pathway as a co-treatment for NK-based immunotherapies, leading AML cells to a more susceptible to apoptosis response. (AU)