MicroRNAs as Modulators of the Immune Response in T-Cell Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukaemia (ALL) is an aggressive haematological tumour driven by the malignant transformation and expansion of B-cell (B-ALL) or T-cell (T-ALL) progenitors. The evolution of T-ALL pathogenesis encompasses different master developmental pathways, including the main role played by Notch in cell fate choices during tissue differentiation. Recently, a growing body of evidence has highlighted epigenetic changes, particularly the altered expression of microRNAs (miRNAs), as a critical molecular mechanism to sustain T-ALL. The immune response is emerging as key factor in the complex multistep process of cancer but the role of miRNAs in anti-leukaemia response remains elusive. In this review we analyse the available literature on miRNAs as tuners of the immune response in T-ALL, focusing on their role in Natural Killer, T, T-regulatory and Myeloid-derived suppressor cells. A better understanding of this molecular crosstalk may provide the basis for the development of potential immunotherapeutic strategies in the leukemia field.

Keywords: Acute lymphoblastic leukaemia; MDSC; Natural Killer cells; Notch; T and regulatory T cells; microRNA.

Figure 1

Common and cell-specific miRNAs in immune cell responders against ALL. Common (dotted-line—) and cell-specific (black line—) miRNAs are depicted in the figure in association with the Natural Killer (NK), T and T-regulatory (Treg), and myeloid derived suppressor (MDSC) cells. Created by Biorender.com.