Expression of Immune Receptors in Response to Chemotherapy Treatment in B and T Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL, however, T-cell ALL tends to be more aggressive and show less promising prognosis. 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% due to resistance developed by malignant cells to chemotherapy. Natural Killer (NK) cells represent the cytotoxic compartment of innate immunity. As opposed to T cells, NK cells can recognize and kill malignant cells without the need for antigen presentation. NK cells currently represent a promising immunotherapy alternative to traditional chemotherapy. They directly kill cancer cells through activation/inhibition signals or through cytokine release and mediating an adaptive response. As targets of interest for our research, we chose LLT1, CD155 and PCNA as NK-inhibitory receptors and CS1, 2B4 as activation receptors. Previously, we have shown a significant decrease of LLT1, 2B4 and CS1 on T lymphoblasts of ALL patients collected from 42 subjects after induction chemotherapy and compared with samples from 20 healthy subjects. Based on the preliminary data, in this study we are investigating the effect of chemotherapy on the expression of those activating and inhibitory receptors. Cell surface protein expression and mRNA expression of these NK receptors pre- and post-Doxorubicin and Vincristine treatment of B and T ALL cell lines have been analyzed. Resistance to chemotherapy is one of the major reasons for failure of treatment in cancer recurrence. However, the cytotoxic potential of NK cells can be harnessed to overcome the chemo-resistance seen in leukemic cells.