Expression of CD163 and HLA-DR molecules on the monocytes in chronic lymphocytic leukemia patients

Kowalska, Wioleta

doi:10.5603/fhc.a2020.0002

Cited by 7 publications

(7 citation statements)

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“…By flow‐cytometric analyses, we revealed a leukaemia‐related remodelling of the myeloid compartment also in the PB, where NC monocytes 29 were shown to be increased in B‐ALL patients compared to HDs. Interestingly, altered monocyte subsets have been previously reported in several solid tumours and more recently in CLL 41 . Our data are in accordance with recent work from Witkowski and colleagues 36 demonstrating an enrichment of the NC monocyte subset in the PB and BM of B‐ALL patients at disease onset, potentially linked to poor disease outcome.…”

Section: Discussionsupporting

confidence: 93%

Monocyte–macrophage polarization and recruitment pathways in the tumour microenvironment of B‐cell acute lymphoblastic leukaemia

et al. 2021

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Summary B‐cell acute lymphoblastic leukaemia (B‐ALL) reprograms the surrounding bone marrow (BM) stroma to create a leukaemia‐supportive niche. To elucidate the contribution of immune cells to the leukaemic microenvironment, we investigated the involvement of monocyte/macrophage compartments, as well as several recruitment pathways in B‐ALL development. Immunohistochemistry analyses showed that CD68‐expressing macrophages were increased in leukaemic BM biopsies, compared to controls and predominantly expressed the M2‐like markers CD163 and CD206. Furthermore, the "non‐classical" CD14+CD16++ monocyte subset, expressing high CX3CR1 levels, was significantly increased in B‐ALL patients' peripheral blood. CX3CL1 was shown to be significantly upregulated in leukaemic BM plasma, thus providing an altered migratory pathway possibly guiding NC monocyte recruitment into the BM. Additionally, the monocyte/macrophage chemoattractant chemokine ligand 2 (CCL2) strongly increased in leukaemic BM plasma, possibly because of the interaction of leukaemic cells with mesenchymal stromal cells and vascular cells and due to a stimulatory effect of leukaemia‐related inflammatory mediators. C5a, a macrophage chemoattractant and M2‐polarizing factor, further appeared to be upregulated in the leukaemic BM, possibly as an effect of PTX3 decrease, that could unleash complement cascade activation. Overall, deregulated monocyte/macrophage compartments are part of the extensive BM microenvironment remodelling at B‐ALL diagnosis and could represent valuable targets for novel treatments to be coupled with classical chemotherapy.

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Section: Discussionsupporting

confidence: 93%

Monocyte–macrophage polarization and recruitment pathways in the tumour microenvironment of B‐cell acute lymphoblastic leukaemia

et al. 2021

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“…The non-classical monocytes constituted the majority of cells lacking HLA-DR expression. Moreover, non-classical monocytes presented low CD163 expression [25]. HLA-DR low/-CD163 low/phenotype is also characteristic for M-MDSC [23].…”

Section: Introductionmentioning

confidence: 92%

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

Kowalska

2020

Folia Histochem Cytobiol.

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Introduction. Myeloid derived suppressor cells (MDSCs) are one of the major components of the tumor microenvironment. The accumulation of MDSCs has been demonstrated in many types of human solid tumors. However, the relevance of this heterogeneous population in hematopoietic malignancies has only recently gained stronger attention. MDSCs are a phenotypically and functionally heterogeneous group of cells. The results of recent studies indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) affects a monocytic MDSC (M-MDSC) subpopulation. This study aimed to analyze the frequency of M-MDSCs with intracellular IL-10 and TGF-b1 expression in newly diagnosed CLL patients. We investigated the potential role of M-MDSCs in CLL by analyzing the level of IL-10 and TGF-b1 expression in circulating M-MDSCs in correlation with clinical and laboratory parameters characterizing disease activity and patients' immune status. Material and methods. Seventy CLL patients and 17 age-matched healthy volunteers were included in this study. Flow cytometric detection of Mo-MDSCs (CD14 + CD11b + CD15-HLA-DR-/low) with intracellular IL-10 and TGF-b1 expression was done. Results. We found a significantly higher median percentage of M-MDSC with IL-10 or TGF-b1 expression in CLL patients than in healthy volunteers. The percentage of M-MDSC with intracellular IL-10 or TGF-b1 expression was significantly lower in CLL patients at stage 0 as compared to the stages I/II and III/IV according to Rai stages. The percentage of M-MDSC with intracellular TGF-b1 expression was significantly higher in ZAP-70-positive and CD38-positive patients compared with ZAP-70-negative and group of CD38-negative ones. There was also a significantly higher percentage of M-MDSC positive for intracellular TGF-b expression in patients carrying the 11q22.3 and/or the 17p13.1 deletion than in patients without these genetic aberrations. The percentage of M-MDSC IL-10-positive and M-MDSC TGF-b1-positive measured at the time of diagnosis was higher in patients requiring therapy as compared to patients without treatment during the observation period. Conclusion. In conclusion, we have shown that an increased percentage of M-MDSC cells producing IL-10 and TGF-b1 in CLL patients may be associated with the suppression of the immune response against CLL. It can be assumed that the increased percentage of M-MDSC with an intracellular expression of IL-10 and TGF-b1 may be used in the future as the factor defining the group of patients with shorter time to onset of treatment.

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“…Besides MΦ, in particular monocytes and dendritic cells (DCs) express CD68 and CD163 ( 30 , 41 ). CD68 is further expressed to varying degrees on granulocytes ( 42 , 43 ).…”

Section: Resultsmentioning

confidence: 99%

Association between spatial distribution of leukocyte subsets and clinical presentation of head and neck squamous cell carcinoma

Netzer,

von Arps-Aubert,

Mačinković

et al. 2024

Front. Immunol.

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BackgroundInteractions between tumor cells and cells in the microenvironment contribute to tumor development and metastasis. The spatial arrangement of individual cells in relation to each other influences the likelihood of whether and how these cells interact with each other.MethodsThis study investigated the effect of spatial distribution on the function of leukocyte subsets in the microenvironment of human head and neck squamous cell carcinoma (HNSCC) using multiplex immunohistochemistry (IHC). Leukocyte subsets were further classified based on analysis of two previously published HNSCC single-cell RNA datasets and flow cytometry (FC).ResultsIHC revealed distinct distribution patterns of leukocytes differentiated by CD68 and CD163. While CD68hiCD163lo and CD68hiCD163hi cells accumulated near tumor sites, CD68loCD163hi cells were more evenly distributed in the tumor stroma. PD-L1hi and PD-1hi cells accumulated predominantly around tumor sites. High cell density of PD-L1hi CD68hiCD163hi cells or PD-1hi T cells near the tumor site correlated with improved survival. FC and single cell RNA revealed high variability within the CD68/CD163 subsets. CD68hiCD163lo and CD68hiCD163hi cells were predominantly macrophages (MΦ), whereas CD68loCD163hi cells appeared to be predominantly dendritic cells (DCs). Differentiation based on CD64, CD80, CD163, and CD206 revealed that TAM in HNSCC occupy a broad spectrum within the classical M1/M2 polarization. Notably, the MΦ subsets expressed predominantly CD206 and little CD80. The opposite was observed in the DC subsets.ConclusionThe distribution patterns and their distinct interactions via the PD-L1/PD-1 pathway suggest divergent roles of CD68/CD163 subsets in the HNSCC microenvironment. PD-L1/PD-1 interactions appear to occur primarily between specific cell types close to the tumor site. Whether PD-L1/PD-1 interactions have a positive or negative impact on patient survival appears to depend on both the spatial localization and the entity of the interacting cells. Co-expression of other markers, particularly CD80 and CD206, supports the hypothesis that CD68/CD163 IHC subsets have distinct functions. These results highlight the association between spatial leukocyte distribution patterns and the clinical presentation of HNSCC.

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Expression of CD163 and HLA-DR molecules on the monocytes in chronic lymphocytic leukemia patients

Cited by 7 publications

References 35 publications

Monocyte–macrophage polarization and recruitment pathways in the tumour microenvironment of B‐cell acute lymphoblastic leukaemia

Monocyte–macrophage polarization and recruitment pathways in the tumour microenvironment of B‐cell acute lymphoblastic leukaemia

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

Association between spatial distribution of leukocyte subsets and clinical presentation of head and neck squamous cell carcinoma

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