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Antohe I, Tanasa MP, Dăscălescu A, et al. The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression. Immunobiology. 2020;226(1):152049doi: 10.1016/j.imbio.2020.152049.
Antohe, I., Tanasa, M. P., Dăscălescu, A., Dănăilă, C., Titieanu, A., Zlei, M., Ivanov, I., Sireteanu, A., & Cianga, P. (2021). The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression. Immunobiology, 226(1), 152049. https://doi.org/10.1016/j.imbio.2020.152049
Antohe, Ion, et al. "The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression." Immunobiology vol. 226,1 (2021): 152049. doi: https://doi.org/10.1016/j.imbio.2020.152049
Antohe I, Tanasa MP, Dăscălescu A, Dănăilă C, Titieanu A, Zlei M, Ivanov I, Sireteanu A, Cianga P. The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression. Immunobiology. 2021 Jan;226(1):152049. doi: 10.1016/j.imbio.2020.152049. Epub 2020 Dec 03. PMID: 33352400.
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Immunobiology. 2021 Jan;226(1):152049. doi: 10.1016/j.imbio.2020.152049. Epub 2020 Dec 03.

The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression.

Immunobiology

Ion Antohe, Mariana Pavel Tanasa, Angela Dăscălescu, Cătălin Dănăilă, Amalia Titieanu, Mihaela Zlei, Iuliu Ivanov, Adriana Sireteanu, Petru Cianga

Affiliations

  1. Haematology Department, "Grigore T. Popa" University of Medicine and Pharmacy, Ia?i, Romania; Haematology Department, Regional Oncology Institute, Ia?i, Romania.
  2. Immunology Department, "Grigore T. Popa" University of Medicine and Pharmacy, Ia?i, Romania.
  3. Immunophenotyping Department, Regional Oncology Institute, Ia?i, Romania.
  4. Molecular Diagnostic Department, Regional Oncology Institute, Ia?i, Romania.
  5. Immunology Department, "Grigore T. Popa" University of Medicine and Pharmacy, Ia?i, Romania. Electronic address: [email protected].

PMID: 33352400 DOI: 10.1016/j.imbio.2020.152049

Abstract

Acute Myeloid Leukaemia (AML) is a neoplasia characterised by rapid proliferation and an increased rate of relapses. The AML blasts display features of antigen-presenting cells (APC), and thus can directly modulate the anti-tumour T cell responses. The bone marrow of a group consisting of 30 newly diagnosed patients and four healthy donors (HD) was investigated for the expression of HLA-DR, several molecules involved in MHC-II antigen-presentation and MHC-II groove editing, like HLA-DM, CD74 and CLIP, as well as a set of immune checkpoint ligands, like ICOS-L, B7.2, PD-L2 and B7-H3. The patients were further characterised for their genetic anomalies and distributed to favourable, intermediate and adverse ELN risk categories. We were able to show that while 23% of our patients displayed a low level of HLA-DR surface expression, all patients displayed higher HLA-DM and CD74 expression compared to HD. However, a higher CLIP expression was noticed only in the HLA-DR low patients. The co-inhibitory PD-L2 and B7-H3 molecules were increased in the cases with normal HLA-DR expression; oppositely, the co-stimulatory ICOS-L and the dual function B7.2 were significantly increased in the cases with HLA-DR low expression. Furthermore, no favourable ELN risk cases were found within the HLA-DR low group. All in all, these data show that the AML with low versus normal HLA-DR expression display different profiles of MHC class II machinery molecules and B7 ligands, which are correlated with distinct ELN stratification. Furthermore, as our study included healthy individuals, it offers valuable information about the expression levels that should be considered as normal for these markers known to cause differences in peptide repertoires, reflected further in distinct T-cells polarisation pathways.

Copyright © 2020 Elsevier GmbH. All rights reserved.

Keywords: AML; Antigen-presentation; HLA; HLA-DM; Immunotherapy; Invariant chain

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