The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

Silva, Isabel Gonçalves; Yasinska, Inna M.; Sakhnevych, Svetlana; Fiedler, Walter; Wellbrock, Jasmin; Bardelli, Marco; Varani, Luca; Hussain, Rohanah; Siligardi, Giuliano; Ceccone, Giacomo; Berger, Steffen; Ushkaryov, Yuri A.; Gibbs, Bernhard F.; Fasler‐Kan, Elizaveta; Sumbayev, Vadim V.

doi:10.1016/j.ebiom.2017.07.018

Cited by 173 publications

(168 citation statements)

References 48 publications

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“…However, interesting results regarding the function of LPHN1 in the etiopathogenesis of AML were published in 2017. Ectopically expressed LPHN1 in AML cells may secure their capability to escape the immune system by inactivating cytotoxic lymphoid cells via the ligand-dependent activation of latrophilin-1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9 (Goncalves Silva et al 2017).…”

Section: Resultsmentioning

confidence: 99%

Overexpression of the ABCB1 drug transporter in acute myeloid leukemia cells is associated with downregulation of latrophilin-1

Kocibalova¹,

Guzyova²,

Imrichova³

et al. 2018

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Finding new markers with appropriate prognostic levels for the differential diagnosis of neoplastic diseases represents an important issue for biomedical research. Recently, latrophilin-1 (LPHN1) was reported to be expressed in human monocytic leukemia cell lines and in primary human acute myeloid leukemia (AML) cells. However, this expression was found to be absent in healthy leukocytes. LPHN1 was therefore considered a novel biomarker of human AML. In previous papers, we established two P-gp-positive variants (SKM-1/VCR and MOLM-13/VCR) of AML cell lines derived from parental human AML cells SKM-1 and MOLM-13 by selection with VCR. The present paper addresses the measurement of LPHN1 expression in SKM-1 and MOLM-13 cells and their P-gp-positive variants. Both parental AML lines were positive for LPHN1 expression at the mRNA and protein levels. However, the expression of LPHN1 at both the mRNA and protein levels was reduced in both P-gp-positive SKM-1/VCR and MOLM-13/VCR variants of AML cells. Interestingly, we observed an elevation of the latrophilin-3 transcript in P-gp-positive variants of AML cell lines. The combined results suggest that alterations in latrophilin expression occur in AML cells expressing P-gp.

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Section: Resultsmentioning

confidence: 99%

Overexpression of the ABCB1 drug transporter in acute myeloid leukemia cells is associated with downregulation of latrophilin-1

Kocibalova¹,

Guzyova²,

Imrichova³

et al. 2018

gpb

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“…78 Furthermore, increased serum levels of Galectin-9 and Tim-3 were observed in the plasma of patients with acute myeloid leukemia and chronic lymphocytic leukemia, turning Galectin-9 into a potential target in leukemia. [79][80][81] Galectin-1 functioning is involved in many signaling pathways leading to anti-inflammatory activities by targeting multiple types of immune cells. 68 In T cells, it is controlling T cell effector function homeostasis by regulating activation, differentiation, survival and cytokine production.…”

Section: Galectinsmentioning

confidence: 99%

Human T cell glycosylation and implications on immune therapy for cancer

Bousser

Meuris

Callewaert

et al. 2020

Human Vaccines & Immunotherapeutics

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Glycosylation is an important post-translational modification, giving rise to a diverse and abundant repertoire of glycans on the cell surface, collectively known as the glycome. When focusing on immunity, glycans are indispensable in virtually all signaling and cell-cell interactions. More specifically, glycans have been shown to regulate key pathophysiological steps within T cell biology such as T cell development, thymocyte selection, T cell activity and signaling as well as T cell differentiation and proliferation. They are of major importance in determining the interaction of human T cells with tumor cells. In this review, we will describe the role of glycosylation of human T cells in more depth, elaborate on the importance of glycosylation in the interaction of human T cells with tumor cells and discuss the potential of cancer immunotherapies that are based on manipulating the glycome functions at the tumor immune interface.

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“…HAVCR2 was reported to be abnormally expressed in T-cell lymphoma, acute myeloid leukemia, hepatitis A and injured nerve tissue. It regulated the activity of target immune cells through NF-κB signaling pathway, mTOR signaling pathway and RET signaling pathway (Prokhorov et al, 2015;Goncalves Silva et al, 2017;Avery et al, 2018). The role of HAVCR2 in nerve injury was shown in patients with spontaneous intracerebral hemorrhage whose increased HAVCR2 expression on CD14+ monocytes was associated with systemic inflammatory response and sub-acute brain injury (Xu et al, 2018).…”

Section: Figure 9 |mentioning

confidence: 99%

The Integrated Transcriptome Bioinformatics Analysis Identifies Key Genes and Cellular Components for Spinal Cord Injury-Related Neuropathic Pain

Huang

Meng

Zhu

et al. 2020

Front. Bioeng. Biotechnol.

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Background: Spinal cord injury (SCI) is one of the most devastating diseases with a high incidence rate around the world. SCI-related neuropathic pain (NeP) is a common complication, whereas its pathomechanism is still unclear. The purpose of this study is to identify key genes and cellular components for SCI-related NeP by an integrated transcriptome bioinformatics analysis. Methods: The gene expression profile of 25 peripheral blood samples from chronic phase SCI patients (E-GEOD-69901) and 337 normal peripheral blood samples were downloaded from ArrayExpress and Genotype-Tissue Expression Portal (GTEx), respectively. A total of 3,368 normal peripheral blood mononuclear cells (PBMC) were download from Sequence Read Archive (SRA713577). Non-parametric tests were used to evaluate the association between all of differential expression genes (DEGs) and SCI-related NeP. CellPhoneDB algorithm was performed to identify the ligand-receptor interactions and their cellular localization among single PBMCs. Transcription factor (TF) enrichment analysis and Gene Set Variation Analysis (GSVA) were used to identify the potential upstream regulatory TFs and downstream signaling pathways, respectively. Co-expression analysis among significantly enriched TFs, key cellular communication genes and differentially expressed signaling pathways were performed to identify key genes and cellular components for SCI-related NeP. Results: A total of 2,314 genes were identified as DEGs between the experimental and the control group. Five proteins (ADRB2, LGALS9, PECAM1, HAVCR2, LRP1) were identified in the overlap of proteins in the significant ligand-receptor interactions of PBMCs and protein-protein interaction (PPI) network based on the DEGs. Only HAVCR2

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The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

Cited by 173 publications

References 48 publications

Overexpression of the ABCB1 drug transporter in acute myeloid leukemia cells is associated with downregulation of latrophilin-1

Overexpression of the ABCB1 drug transporter in acute myeloid leukemia cells is associated with downregulation of latrophilin-1

Human T cell glycosylation and implications on immune therapy for cancer

The Integrated Transcriptome Bioinformatics Analysis Identifies Key Genes and Cellular Components for Spinal Cord Injury-Related Neuropathic Pain

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