Differential expression of immune receptors in pediatric Acute Lymphoblastic Leukemia (ALL)

Abstract

Abstract Acute Lymphoblastic Leukemia (ALL) represents the most common pediatric cancer. Significant improvements in chemotherapy regimens caused a leap in the 5-year survival rates to surpass 90%. However, relapse significantly lowers the chances of survival to less than 50% in some cases due to resistance developed by malignant cells to chemotherapy. Natural Killer (NK) cells are a promising immunotherapy alternative for their ability to recognize and kill malignant cells directly through activation or inhibition signals or through cytokine release. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 that can activate or inhibit NK cells upon the interaction with their ligands. In this study, the expression of 2B4, CS1, LLT1, NKp30 and NKp46 was determined in pediatric ALL and healthy subjects. Whole blood was collected from 42 pediatric ALL subjects before and after induction chemotherapy and the surface expression of receptors/ligand on T-cells, B-cells, monocytes, and NK-cells was compared with blood samples from 20 healthy subjects. The flow cytometry data showed a significant increase in CS1 and NKp46 expression on monocytes and LLT1 in T cells and monocytes of ALL subjects before treatment. A decrease of LLT1, 2B4, CS1 and NKp46 on T-cells of ALL subjects was also observed after treatment along with elevated expression of LLT1 on ALL subjects’ NK-cells before and after treatment. Furthermore, mRNA data showed altered expression of receptors in ALL subjects pre and post induction chemotherapy treatment. The results indicate that the differential expression of the receptors/ligand may play a role in the T cell and NK-cell mediated immune surveillance of pediatric ALL. Supported by funds from Cancer Research Foundation of North Texas and Team Connor Childhood Cancer Foundation