Objective: Myeloid-derived suppressor cells (MDSCs) facilitate tumor growth and development by suppressing T cell function; however, their role in acute myeloid leukemia (AML) remains unclear. Here, we investigated the immunosuppressive role and prognostic value of blasts with an MDSC-like phenotype.
Methods: CD11b+ CD33+ HLA-DR- MDSC-like blasts from bone marrow mononuclear cells of patients with AML were analyzed. To investigate their T cell-suppressing function, MDSC-like blasts were isolated using flow cytometry and co-cultured with CD8+ cytotoxic T cells and NB4 leukemic cells. Treatment outcomes were then compared between the MDSC-like blasts low (≤9.76%) and high (>9.76%) groups to identify clinical significance.
Results: MDSC-like blasts showed higher expression of arginase-1 and inducible nitric oxide synthase. Isolated MDSC-like blasts significantly suppressed CD8+ T cell proliferation induced by phytohemagglutinin A. NB4 cell proliferation was significantly suppressed upon co-culture with CD8+ cytotoxic T cells and partially restored upon co-culture with MDSC-like blasts. Patients with high MDSC-like blasts at diagnosis showed substantially shorter overall survival and leukemia-free survival relative to low MDSC-like blasts patients, with subgroup analysis showing statistically significant differences in patients not receiving allogeneic hematopoietic stem cell transplantation.
Conclusion: We demonstrated that MDSC-like blasts drive AML-specific immune-escape mechanisms by suppressing T cell proliferation and restoring T cell-suppressed NB4 cell proliferation, with clinically higher fractions of MDSC-like blasts at diagnosis resulting in poor prognosis.
Keywords: acute myeloid leukemia; arginase; inducible nitric oxide synthase; myeloid-derived suppressor cells; prognosis.
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.