Decrease and impaired function of circulating mucosa-associated invariant T cells in acute myeloid leukemia

Abstract

Abstract Acute myeloid leukemia (AML) is an aggressive cancer characterized by significantly low mucosa-associated invariant T (MAIT) cells. Though the reasons for their decline and their functional implications in AML are yet to be explored, their levels have been reported to be associated with the prognosis of the disease. This study aimed to characterize the frequency, phenotype, and function of circulating MAIT cells during AML progression. Our results showed that the levels of circulating MAIT cells in patients with AML (AML-MAIT cells) were lower compared to healthy donors, and they were found to express high levels of HLA-DR, PD-1, and TIM-3, indicating that the AML-MAIT cells exhibited an activated and exhausted phenotype. AML-MAIT cells expressed higher KLRG1 and CD57 levels, indicating that circulating AML-MAIT cells displayed a senescent phenotype. The observation that MAIT cells in patients with AML had both senescent and pro-apoptotic phenotypes may underlie the decrease in circulating AML-MAIT cells. Additionally, circulating AML-MAIT cells produced less IFN-γ, TNF-α, and granzyme B, suggesting dysfunctional anti-tumor immunity. Moreover, we found AML patients with adverse cytogenetic have fewer MAIT cells than that with intermediate/favorable cytogenetic. In conclusion, circulating MAIT cells are decreased due to exhausted and senescent phenotypes and are functionally impaired in patients with AML. Therefore, enhancing circulating MAIT cells might be an attractive therapeutic strategy for patients with AML.