HLA-G Expression on Blasts and Tolerogenic Cells in Patients Affected by Acute Myeloid Leukemia

Author:

Locafaro Grazia12ORCID,Amodio Giada1ORCID,Tomasoni Daniela1,Tresoldi Cristina3ORCID,Ciceri Fabio4,Gregori Silvia1ORCID

Affiliation:

1. San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute (HSR-DREaM-GENE), Via Olgettina 58, 20132 Milan, Italy

2. Ph.D Program in Translational and Molecular Medicine (DIMET), University of Milan-Bicocca, Piazza della Scienza 3, 20126 Milan, Italy

3. Immunohematology Blood Transfusion Service (S.I.M.T.), San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy

4. Hematology and Bone Marrow Transplantation Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute (HSR-DREaM-GENE), Via Olgettina 58, 20132 Milan, Italy

Abstract

Human Leukocyte Antigen-G (HLA-G) contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role of HLA-G expression and functions in Acute Myeloid Leukemia (AML) is still controversial. Our group identified a subset of tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10 are present in the peripheral blood and are essential in promoting and maintaining tolerance via the induction of adaptive T regulatory (Treg) cells. We investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC-10 and CD4+T cells in the peripheral blood of AML patients at diagnosis. Moreover, we explored the possible influence of the 3′ untranslated region (3′UTR) ofHLA-G, which has been associated with HLA-G expression, on AML susceptibility. Results showed that HLA-G-expressing DC-10 and CD4+T cells are highly represented in AML patients with HLA-G positive blasts. None of the HLA-G variation sites evaluated was associated with AML susceptibility. This is the first report describing HLA-G-expressing DC-10 and CD4+T cells in AML patients, suggesting that they may represent a strategy by which leukemic cells escape the host’s immune system. Further studies on larger populations are required to verify our findings.

Funder

Associazione Italiana per la Ricerca sul Cancro

Publisher

Hindawi Limited

Subject

Immunology,General Medicine,Immunology and Allergy

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