The effects of released exosomes from stimulated NK-Cells with IL15 on the apoptosis of human acute myeloid leukemia cell line (HL-60)

Abstract

Acute myeloid leukemia (AML) is one of the most common hematologic malignancies, especially in adults over 60 years of age, for which chemotherapy-based methods are used for its treatment. These drugs have effects such as excessive fatigue, nausea, severe hair loss, etc. For this reason, the attention of researchers has been drawn to alternative treatments in order to achieve complete recovery of patients and fewer complications. Immunotherapy is one of these methods in which, by making changes in immune cells, it strengthens the body's immune system to fight tumor cells. However, due to reasons such as different ways of cancer cells to escape from the immune system and the compounds present in the tumor space, this method of treatment faces challenges that make it impossible to achieve a favorable result. Natural killer cells or NK cells are among the first immune cells that detect the existence of a tumor. These cells, with the help of cytotoxic proteins and cell-killing receptors, cause the destruction of the cancer cell and become more active and deadly due to some cytokines, such as IL-2 and IL-15. However, due to exhaustion and suppression by compounds in the tumor space, they are not capable of eradicating cancer cells and need changes to be used in immunotherapy. Exosomes are nanoparticles that are secreted from most cells and are responsible for transmitting signals and genetic information between cells. These particles, in addition to their unique characteristics, also have some of the characteristics of the mother cell. According to this point and the research done, exosomes derived from NK cells have characteristics that may make them effective for use in immunotherapy. Exosomes obtained from NK cells contain components of NK cells such as perforin, NKG2D and Fas-L. The small size, the tendency to be present in an acidic environment and the stability of these nanoparticles make cancer cells easily absorb them and make these particles more lethal to cancer cells than their parent cells. Material and Methods: In this research, using the ultracentrifuge method, exosome was extracted from two groups of NK-92 cells, one of which was a control group and the other was stimulated by IL-15, and then with HL-60 cells, which belong to a type of cancer. It is blood, we fight together in different concentrations. Finally, with the help of annexin test, we measure the amount of apoptosis. Results: The findings of this research show that exosomes obtained from NK cells stimulated with IL-15 may be more toxic and efficient than those obtained from unstimulated cells and lead to more apoptosis in target cells.