Arginase-1 mRNA expression correlates with myeloid-derived suppressor cell levels in peripheral blood of NSCLC patients

Heuvers, Marlies E.; Muskens, Femke; Bezemer, Koen; Lambers, Margaretha; Dingemans, Anne‐Marie C.; Groen, Harry J.M.; Smit, Egbert F.; Hoogsteden, Henk C.; Hegmans, Joost P.; Aerts, Joachim

doi:10.1016/j.lungcan.2013.06.005

Cited by 65 publications

(66 citation statements)

References 33 publications

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“…29 Likewise, in a previous study we showed that arginase-1 is expressed in PBMCs in much larger amounts in lung cancer patients than in healthy controls. 23,30 Our finding that ILT3 is upregulated on MDSCs of NSCLC patients is in agreement with functional differences with regard to immunosuppression by MDSCs in NSCLC patients and healthy controls.…”

Section: Discussionsupporting

confidence: 79%

“…23 Accordingly, in the cohort used in this study the frequencies of both MO-MDSCs and PMN-MDSCs in peripheral blood were significantly higher in patients than in healthy controls, as shown in Figure 1B. ILT3 is expressed by subpopulations of MDSCs ILT3 expression could be detected on both PMN-MDSCs and MO-MDSCs ( Fig. 2A).…”

Section: Levels Of Mo-mdscs and Pmn-mdscs Are Elevated In Stage IV Nsmentioning

confidence: 64%

“…Table 1 shows the characteristics of the 105 NSCLC study participants and 20 healthy controls (HC) that were included in our analyses. The patient characteristics of this study cohort were similar to those of the total NVALT12 population, 23 therefore no selection bias was introduced.…”

Section: Resultsmentioning

confidence: 99%

“…The gating strategy for the 2 populations is presented in Figure 1A and was performed as previously described. 23 First, mature granulocytes were excluded based on their CD16…”

Section: Levels Of Mo-mdscs and Pmn-mdscs Are Elevated In Stage IV Nsmentioning

confidence: 99%

“…21,22 We have previously have shown increased levels of MDSCs in patients with treatment-na€ ıve Stage IV non-small cell lung carcinoma (NSCLC). 23 Because MDSCs have the ability to induce immune suppression, we hypothesized that ILT3 expression could be part of a yet unidentified mechanism by which MDSCs mediate immune escape. Therefore, we aimed to assess the expression of ILT3 on MDSCs of lung cancer patients with advanced disease before the start of chemotherapy and evaluate its effect on clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

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Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

et al. 2015

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Myeloid-derived suppressor cells (MDSCs) play an important role in immune suppression and accumulate under pathologic conditions such as cancer and chronic inflammation. They comprise a heterogeneous population of immature myeloid cells that exert their immunosuppressive function via a variety of mechanisms. Immunoglobulin-like transcript 3 (ILT3) is a receptor containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) that can be expressed on antigen-presenting cells and is an important regulator of dendritic cell tolerance. ILT3 exists in a membrane-bound and a soluble form and can interact with a yet unidentified ligand on T cells and thereby induce T-cell anergy, regulatory T cells, or T suppressor cells. In this study, we analyzed freshly isolated peripheral blood mononuclear cells (PBMCs) of 105 patients with non-small cell lung cancer and 20 healthy controls and demonstrated for the first time that ILT3 is expressed on MDSCs. We show that increased levels of circulating MDSCs correlate with reduced survival. On the basis of ILT3 cell surface expression, an ILT3 low and ILT3 high population of polymorphonuclear (PMN)-MDSCs could be distinguished. Interestingly, in line with the immunosuppressive function of ILT3 on dendritic cells, patients with an increased proportion of PMN-MDSCs and an increased fraction of the ILT3 high subset had a shorter median survival than patients with elevated PMN-MDSC and a smaller ILT3 high fraction. No correlation between the ILT3 high subset and other immune variables was found. ILT3 expressed on MDSCs might reflect a previously unknown mechanism by which this cell population induces immune suppression and could therefore be an attractive target for immune intervention.

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Section: Discussionsupporting

confidence: 79%

Section: Levels Of Mo-mdscs and Pmn-mdscs Are Elevated In Stage IV Nsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

“…The gating strategy for the 2 populations is presented in Figure 1A and was performed as previously described. 23 First, mature granulocytes were excluded based on their CD16…”

Section: Levels Of Mo-mdscs and Pmn-mdscs Are Elevated In Stage IV Nsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

et al. 2015

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Functional Flow Cytometry to Predict PD‐L1 Conformational Changes

Salvia,

Rico,

Ward

et al. 2023

Current Protocols

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The programmed cell death protein 1/programmed cell death protein ligand 1 (PD‐1/PD‐L1) axis is one of the most widely recognized targets for cancer immunotherapy. Importantly, PD‐L1 conformational changes can hinder target binding when living cells are used. Antibody affinity, equilibrium binding, association and dissociation rates, and other affinity‐related constants are fundamental to ensure target saturation. Here, PD‐L1 changes in conformation and their potential impact on PD‐L1 function and mutation are explored. Specifically, we present detailed flow cytometry procedures to analyze PD‐L1 reactivity in myeloid‐derived suppressor cells (MDSCs). This approach can also be used to study the contribution of protein conformational changes in living cells. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Sample preparation for PD‐L1+ myeloid‐derived suppressor cells detection by flow cytometryBasic Protocol 2: Protocol preparation, sample acquisition, and gating strategy for flow cytometric screening of PD‐L1+ myeloid‐derived suppressor cells in patients with lung cancerSupport Protocol 1: Bioinformatic tools for the analysis of flow cytometric data

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Complexity and challenges in defining myeloid-derived suppressor cells

et al. 2014

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Study of myeloid cells endowed with suppressive activity is an active field of research which has particular importance in cancer, in view of the negative regulatory capacity of these cells to the host's immune response. The expansion of these cells, called myeloid-derived suppressor cells (MDSCs), has been documented in many models of tumor-bearing mice and in patients with tumors of various origin, and their presence is associated with disease progression and reduced survival. For this reason, monitoring this type of cell expansion is of clinical importance, and flow cytometry is the technique of choice for their identification. Over the years, it has been demonstrated that MDSCs comprise a group of immature myeloid cells belonging both to monocytic and granulocytic lineages, with several stages of differentiation; their occurrence depends on tumor-derived soluble factors, which guide their expansion and determine their block of differentiation. Because of their heterogeneous composition, accurate phenotyping of these cells requires a multicolor approach, so that the expansion of all MDSC subsets can be appreciated.This review article focuses on identifying MDSCs and discusses problems associated with phenotyping circulating and tumor-associated MDSCs in humans and in mouse models. © 2014 The Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.

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Arginase-1 mRNA expression correlates with myeloid-derived suppressor cell levels in peripheral blood of NSCLC patients

Cited by 65 publications

References 33 publications

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

Functional Flow Cytometry to Predict PD‐L1 Conformational Changes

Complexity and challenges in defining myeloid-derived suppressor cells

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