Dendritic cells in hematological malignancies

Galati, Domenico; Corazzelli, Gaetano; Filippi, Rosaria De; Pinto, Antonio

doi:10.1016/j.critrevonc.2016.10.006

Cited by 24 publications

(31 citation statements)

References 127 publications

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“…Consistent results were found in HL for CD83 pos myeloid DCs [27] and in DLBCL for CD1a pos DCs [28]. Altogether, these results suggested DCs mediate anti-tumor immunity [26].…”

Section: In Germinal Center B-cell Lymphomas Myeloid Regulatory Cellsupporting

confidence: 77%

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Regulatory myeloid cells: an underexplored continent in B-cell lymphomas

Roussel

Irish

Ménard

et al. 2017

Cancer Immunol Immunother

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In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the clinical impact of this phenotype remains controversial. Across cancer types, myeloid cells are primarily thought to function as immune suppressors during tumor initiation and maintenance, but the biological mechanisms behind the myeloid signatures are still poorly understood in germinal center B-cell lymphomas. Herein, we describe the role and clinical relevance of myeloid cells in B-cell lymphoma and propose innovative approaches to decipher this complex cellular compartment. Indeed, characterization of this heterogeneous cell ecosystem has been largely accomplished with "low-resolution" approaches like morphological evaluation and immunohistochemistry, where cells are characterized using a few proteins and qualitative metrics. High-resolution, quantitative approaches, such as mass cytometry, are valuable to better understand myeloid cell diversity, functions, and to identify potential targets for novel therapies.

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“…Consistent results were found in HL for CD83 pos myeloid DCs [27] and in DLBCL for CD1a pos DCs [28]. Altogether, these results suggested DCs mediate anti-tumor immunity [26].…”

Section: In Germinal Center B-cell Lymphomas Myeloid Regulatory Cellsupporting

confidence: 77%

“…Few studies have evaluated associations between DCs and B-cell lymphoma prognosis. High numbers of plasmacytoid DCs in FL tumors were correlated with a good prognosis [26].…”

Section: In Germinal Center B-cell Lymphomas Myeloid Regulatory Cellmentioning

confidence: 99%

Regulatory myeloid cells: an underexplored continent in B-cell lymphomas

Roussel

Irish

Ménard

et al. 2017

Cancer Immunol Immunother

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“…The quantitative reduction of blood DCs and their dysfunction, due either to an impaired maturation capacity or allostimulatory activity, have been documented in different haematological malignancies, such as chronic lymphocytic leukaemia (Orsini et al , ), hairy cell leukaemia (Bourguin‐Plonquet et al , ), acute lymphoblastic leukaemia (Mami et al , ), multiple myeloma (Ratta et al , ; Brimnes et al , ) and chronic myeloid leukaemia (Mohty et al , ; Dong et al , ; Boissel et al , ; Galati et al , ).…”

Section: Discussionmentioning

confidence: 99%

Circulating dendritic cells deficiencies as a new biomarker in classical Hodgkin lymphoma

et al. 2018

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Summary No robust biomarkers have been yet validated to identify the recurrence of disease in classical Hodgkin Lymphoma (cHL) patients upon induction treatment. The relevance of the inflammatory microenvironment in cHL prompted us to investigate the key immunomodulator myeloid dendritic cells type‐1 (mDC1), type‐2 (mDC2) and plasmacytoid dendritic cells (pDC). Blood DC levels were assessed in 52 newly diagnosed patients through multiparametric flow‐cytometry. All but two patients received ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). The median counts of all DC subsets were lower in cHL patients than in healthy controls (P < 0·001). Median mDC counts were inferior for the advanced vs early stage patients for both mDC1s and mDC2s (P = 0·008; P = 0·0007 respectively). Also, median mDC2 counts were reduced in case of bulky (P = 0·0004) and extra‐nodal (P = 0·046) disease. Patients with B symptoms had lower levels for mDC1s (P = 0·046), mDC2s (P = 0·009) and pDCs (P = 0·040). All the DC subtypes increased at the end of treatment in 26 patients (P < 0·001): 4·6‐fold for mDC1, 2·4‐fold for mDC2, 4·5‐fold for pDC and aligned DCs subsets with the reference frequencies and the interquartile ranges of the controls. In conclusion, DCs may contribute to the disturbed immunological interplay typical of cHL, prompting a further evaluation of their value as a potential new biomarker.

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“…Interestingly, pDCs are known to regulate B cell differentiation and Ig secretion through CD70 and IL-6 [32]. The lower number of pDCs locally in concurrence with B cell infiltrate in IOI could therefore be driven by a negative feedback loop mediated by self-maintaining B-cell expansion, or pDC differentiation and activation affecting surface marker expression [19]. In blood, however, we observed no correlation between DC subtypes and the B-cell compartment.…”

Section: Discussionmentioning

confidence: 58%

cDC2 and plasmacytoid dendritic cells diminish from tissues of patients with non‐Hodgkin orbital lymphoma and idiopathic orbital inflammation

et al. 2020

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Non‐Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology. To investigate the immune cell composition of these diseases, we performed standardized 29 parameter flow cytometry phenotyping in peripheral blood mononuclear cells of 18 NHOL patients, 21 IOI patients, and 41 unaffected controls. Automatic gating by FlowSOM revealed decreased abundance of meta‐clusters containing dendritic cells in patients, which we confirmed by manual gating. A decreased percentage of (HLA‐DR+CD303+CD123+) plasmacytoid dendritic cells (pDC) in the circulation of IOI patients and decreased (HLA‐DR+CD11c+CD1c+) conventional dendritic cells (cDC) type‐2 for IOI patients were replicated in an independent cohort of patients and controls. Meta‐analysis of both cohorts demonstrated that pDCs are also decreased in blood of NHOL patients and highlighted that the decrease in blood cDC type‐2 was specific for IOI patients compared to NHOL or controls. Deconvolution‐based estimation of immune cells in transcriptomic data of 48 orbital biopsies revealed a decrease in the abundance of pDC and cDC populations within the orbital microenvironment of IOI patients. Collectively, these data suggest a previously underappreciated role for dendritic cells in orbital disorders.

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Dendritic cells in hematological malignancies

Cited by 24 publications

References 127 publications

Regulatory myeloid cells: an underexplored continent in B-cell lymphomas

Regulatory myeloid cells: an underexplored continent in B-cell lymphomas

Circulating dendritic cells deficiencies as a new biomarker in classical Hodgkin lymphoma

cDC2 and plasmacytoid dendritic cells diminish from tissues of patients with non‐Hodgkin orbital lymphoma and idiopathic orbital inflammation

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