Altered microRNA expression profile is linked to T-cell exhaustion-related pathways in pediatric patients with acute lymphoblastic leukemia.

Background: Although the phenotype and functions of exhausted T cells in several cancers have been identified, the involved molecular mechanisms remain to be further elucidated. In this regard, we have recently reported that the immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (T), share common dysregulated miRNAs that target specific immunosuppressive pathways in patients with in acute lymphoblastic leukemia (ALL).

Aim: In this study, we aimed to further explore whether similar dysregulation in miRNA expression is linked to T cell exhaustion and dysfunctionality in B cell ALL patients.

Methods: Peripheral blood samples from pediatric patients with ALL were recruited before and after induction chemotherapy as well as from healthy donors. Affymetrix microarray platform was used for miRNA profiling, and qRT-PCR was used to validate the expression of certain miRNAs that are related to T cell exhaustion. Bioinformatics analysis was performed to explore whether the dysregulated miRNAs were linked to T-cell exhaustion related pathways.

Results: A total of 516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Furthermore, among the total analyzed miRNAs, 10 were found to be linked to the key genes implicated in three exhaustion-related pathways; TGF-β, FOXO, and MAPK, as revealed by miR-pathway analysis. Moreover, qRT-PCR analysis showed similar expression pattern to those obtained by microarray analysis.

Conclusion: Our pilot study suggests the implication of certain miRNAs in T cell exhaustion pathways via targeting the specific key genes in those pathways.