Acute myeloid leukemia (AML) is a cancer originating from cells of the bone marrow and remains difficult to cure due to relapses. There have been significant advances in the development of immunotherapeutic approaches to various types of cancer. Immunotherapy stimulates the patient’s immune system to destroy cancer cells without the harmful adverse effects seen with conventional chemotherapy.
Cytotoxic T cells are potent immune cells with the ability to eliminate cancer stem cells. In vitro experiments have shown that Leukemia-derived cytotoxic T cell lines can inhibit the proliferation of leukemic progenitor cells. Other studies showed that chemotherapy can make tumor cells more vulnerable to the actions of cytotoxic T cells. Therefore, researchers conducted a study to determine the effects of combination therapy with AML-specific cytotoxic T cells and a chemotherapeutic agent commonly used for hematological malignancies (cytarabine). They cultured peripheral blood lymphocytes obtained from healthy donors with Kasumi-3 cells (a leukemic cell line). The identification of AML-cytotoxic T cells was achieved via antibody-based flow cytometry.
Kasumi-3 cells were treated in vitro with cytarabine, cytotoxic T cells, a combination of cytarabine and the T cells, or left untreated. Apoptosis of Kasumi-3 cells was determined using an Annexin V-FITC Apoptosis assay kit. The results showed that treatment with cytarabine lead to apoptosis of just over 20% of the Kasumi-3 cells, treatment with cytotoxic T cells caused an apoptosis rate of 26%, but the combination treatment caused apoptosis in over 37% of the kamusi-3 cells. This demonstrated a significant increase in apoptosis with the combination treatment.
To determine the basis of the synergistic effect of the combination treatment, differences in Bcl-2 expression (an important regulator of apoptosis) between the 3 treatments were studied using western blotting. The western blot results showed that Bcl-2 was downregulated with all treatments, but more strongly with the combination treatment. This suggests that the downregulation of Bcl-2 may mediate the synergistic effect of the combination AML-cytotoxic T cell/cytarabine effects on apoptosis. This work provides the basis of future studies to better develop this treatment for AML in regards to specificity and the optimal combinations that are the most effective to treat AML.
Deng, R., Fan, F., Yi, H., Fu, L., Zeng, Y., & Wang, Y. et al. (2017). Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression. Experimental And Therapeutic Medicine. doi:10.3892/etm.2017.4620