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

Antohe, Ion; Pavel-Tanasa, Mariana; Dăscălescu, Angela; Danaı̈la, Catalin; Titieanu, Amalia; Zlei, Mihaela; Ivanov, Iuliu; Sireteanu, Adriana; Cianga, Petru

doi:10.1016/j.imbio.2020.152049

Cited by 9 publications

(9 citation statements)

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“…We also observed that the motif WPH of P6 in the HLA‐DRB1*15:03 allele was only found in ALL patients with a low frequency ( n = 7), which could likely explain the failure to reach statistical significance. The HLA‐DRB1*15:03 allele was previously implicated in the development of malignancies including ALL and prostate cancer 24,28 . In terms of HLA‐DQB1 variability, the motif YYVSY in P9 of the HLA‐DQB1*05:02/04/05 alleles, as well as serine 57 in the P9 of various alleles including HLA‐DQB1*05:02 was characteristic of ALL patients.…”

Section: Discussionmentioning

confidence: 96%

“…32 Some in-vitro studies involving different compounds and PBP have been performed in leukaemic cells. 24,33 Structural modelling has shown that amino acid substitutions might alter the peptide preference of the ligand-binding pocket. 11 Interestingly, peptides binding to HLA class II molecules are frequently viewed as mergers of detached anchor residue preferences for P4 and P9.…”

Section: Discussionmentioning

confidence: 99%

“…Further, the role of the complex interplay between leukaemic blasts and their microenvironment has been useful in guiding and personalizing therapeutic approaches 32 . Some in‐vitro studies involving different compounds and PBP have been performed in leukaemic cells 24,33 . Structural modelling has shown that amino acid substitutions might alter the peptide preference of the ligand‐binding pocket 11 .…”

Section: Discussionmentioning

confidence: 99%

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Comparative analysis of the variability of the human leukocyte antigen peptide‐binding pockets in patients with acute leukaemia

et al. 2022

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Summary The association between acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) and the human leukocyte antigens (HLA) has rarely been studied in terms of diversity of peptide‐binding pockets. The objective of this study was to analyse whether motifs of HLA class I and class II peptide‐binding pockets and/or their amino acid positions were differentially associated with ALL and AML. We included 849 patients from the Eurocord/European Blood and Marrow Transplant registry. The HLA peptide‐binding pockets whose amino acid variability was analysed were B and F for HLA class I, P4, P6, and P9 for HLA‐DRB1, and P4 and P9 for HLA‐DQB1. The motif RFDRAY in P4 of HLA‐DRB1*16:01/02/03/05 alleles and the motif YYVSY in P9 of HLA‐DQB1*05:02/04/05 alleles, were statistically associated with ALL (corrected p value [pc] = 0.001 and pc = 0.035 respectively). The frequency of serine 57 in the P9 of HLA‐DQB1 was higher in ALL (odds ratio 2.09, 95% confidence interval: 1.27–3.44; pc = 0.037). Our analysis suggests that specific motifs in terms of HLA class II pockets and amino acids might be unique to ALL. The associations identified in this study encourage further investigation oF the role of HLA peptide‐binding pockets and their amino acids in immune processes underpinning acute leukaemia and ultimately in immunotherapy settings.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparative analysis of the variability of the human leukocyte antigen peptide‐binding pockets in patients with acute leukaemia

et al. 2022

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“…IFN-γ, APM, and hypoxia pathways were correlated with high response to immunotherapy [ 44 , 45 ], while FGFR3, β-catenin, PPAR-γ, and VEGFA pathways were activated in the non-inflamed tumors [ 46 , 47 ]. The interplays between HLA-DRA and IFN-γ signature as well as the APM signal were clear [ 48 , 49 ]. For example, IFN-γ could increase the expression of the HLA-DRA [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC

et al. 2022

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Background Immune checkpoint blockade (ICB) only works well for a certain subset of patients with non-small cell lung cancer (NSCLC). Therefore, biomarkers for patient stratification are desired, which can suggest the most beneficial treatment. Methods In this study, three datasets (GSE126044, GSE135222, and GSE136961) of immunotherapy from the Gene Expression Omnibus (GEO) database were analyzed, and seven intersected candidates were extracted as potential biomarkers for ICB followed by validation with The Cancer Genome Atlas (TCGA) dataset and the in-house cohort data. Results Among these candidates, we found that human leukocyte antigen-DR alpha (HLA-DRA) was downregulated in NSCLC tissues and both tumor and immune cells expressed HLA-DRA. In addition, HLA-DRA was associated with an inflamed tumor microenvironment (TME) and could predict the response to ICB in NSCLC. Moreover, we validated the predictive value of HLA-DRA in immunotherapy using an in-house cohort. Furthermore, HLA-DRA was related to the features of inflamed TME in not only NSCLC but also in most cancer types. Conclusion Overall, HLA-DRA could be a promising biomarker for guiding ICB in NSCLC.

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“…DCs, monocytes, and macrophages have long been identified as antigen-presenting cells in circulation and in tissues [40][41][42] . APC, reacted with antigen, presented MHC II groove-bound peptides to CD4 + T cells that share the same allele, provoking immune responses 43 . Our CyTOF results revealed aGVHD-specific immune cell subsets, especially Tax + CD68 + APCs.…”

Section: Htlv-1 Only Found In Agvhd Patients After Liver Transplantationmentioning

confidence: 99%

HTLV-1 infection of donor-derived T cells might promote acute graft-versus-host disease following liver transplantation

Shen

Wang

et al. 2022

Nat Commun

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Acute graft versus host disease (aGVHD) is a rare, but severe complication of liver transplantation (LT). It is caused by the activation of donor immune cells in the graft against the host shortly after transplantation, but the contributing pathogenic factors remain unclear. Here we show that human T cell lymphotropic virus type I (HTLV-1) infection of donor T cells is highly associated with aGVHD following LT. The presence of HTLV-1 in peripheral blood and tissue samples from a discovery cohort of 7 aGVHD patients and 17 control patients is assessed with hybridization probes (TargetSeq), mass cytometry (CyTOF), and multiplex immunohistology (IMC). All 7 of our aGVHD patients display detectable HTLV-1 Tax signals by IMC. We identify donor-derived cells based on a Y chromosome-specific genetic marker, EIF1AY. Thus, we confirm the presence of CD4+Tax+EIF1AY+ T cells and Tax+CD68+EIF1AY+ antigen-presenting cells, indicating HTLV-1 infection of donor immune cells. In an independent cohort of 400 patients, we verify that HTLV-1 prevalence correlates with aGVHD incidence, while none of the control viruses shows significant associations. Our findings thus provide new insights into the aetio-pathology of liver-transplantation-associated aGVHD and raise the possibility of preventing aGVHD prior to transplantation.

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

Cited by 9 publications

References 50 publications

Comparative analysis of the variability of the human leukocyte antigen peptide‐binding pockets in patients with acute leukaemia

Comparative analysis of the variability of the human leukocyte antigen peptide‐binding pockets in patients with acute leukaemia

HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC

HTLV-1 infection of donor-derived T cells might promote acute graft-versus-host disease following liver transplantation

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