Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy

Gorp, Hanne Van; Delputte, Peter; Nauwynck, Hans

doi:10.1016/j.molimm.2010.02.008

Cited by 308 publications

(281 citation statements)

References 146 publications

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“…24 CD163 is a monocyte/macrophage-specific marker that is mainly expressed on M2 macrophages as well as on immune suppressive DCs. 14,[25][26][27][28] Our results demonstrate that under healthy conditions, intraepithelial myeloid cells are absent whereas in the stroma M2 macrophages dominate. The changes to vulvar dysplasia are characterized by an increase in both intraepithelial and stromal mature CD141 M1 and M2 macrophages.…”

mentioning

confidence: 56%

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Esch

Poelgeest

Trimbos

et al. 2014

Intl Journal of Cancer

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Human papilloma virus (HPV)-induced usual-type vulvar intraepithelial neoplasia (uVIN) is infiltrated by myeloid cells but the type and role of these cells is unclear. We used triple immunofluorescent confocal microscopy to locate, identify and quantify myeloid cells based on their staining pattern for CD14, CD33 and CD163 in a cohort of 43 primary and 20 recurrent uVIN lesions, 21 carcinomas and 26 normal vulvar tissues. The progressive course of uVIN is characterized by an increase in both intraepithelial and stromal mature M1 and M2 macrophages. While the M2 macrophages outnumber M1 macrophages in healthy controls and uVIN, they are matched in number by M1 macrophages in cancer. Importantly, uVIN patients with a dense intraepithelial infiltration with mature CD141 macrophages (irrespective of M1 or M2 type) displayed approximately a six times higher risk to develop a recurrence and a high number of these cells constituted an independent prognostic factor for recurrence. In addition, a dense intraepithelial CD141 cell infiltration was associated with high numbers of intraepithelial CD41 Tregs and low numbers of stromal CD81TIM31 T cells. Patients with low numbers of intraepithelial CD141 cells and high numbers of stromal CD81TIM31 cells showed the best recurrence-free survival. These data clearly show the importance of the local immune response in HPV-induced vulvar neoplasia and may be of help in predicting the prognosis of patients or their response to immunotherapy.Usual-type vulvar intraepithelial neoplasia (uVIN) lesions are caused by a persistent high-risk human papilloma virus (HPV) infection (mainly HPV 16) and are characterized by high recurrences, a low spontaneous regression rate of 1.5% and a malignant potential of 3-4% in treated patients. [1][2][3] Treatment of uVIN lesions is indispensable since 80% of patients suffer from symptoms as pruritis and pain. 2-4 Conventional treatment consistent of potential disfiguring surgical interventions is associated with psychosexual problems and is increasingly replaced by either standardized immunotherapy with imiquimod or immunotherapy in experimental setting by therapeutic vaccination or photodynamic therapy, with promising clinical successes. [2][3][4][5][6][7][8] The incidence of hrHPV-induced dysplasia is increased in immunocompromised patients highlighting the essential role of the immune system in viral clearance. 9,10 Spontaneous regression of HPV is associated with systemic HPV-specific CD41 and CD81 immune responses, however in most of the patients with uVIN these T cell responses are either weak or absent. 11,12 In addition, the local innate immune cell environment is known to influence innate and adaptive immune responses in tumors. 13,14 Monocytes are innate immune cells which can differentiate into dendritic cells (DCs) or macrophages in response to local factors. 13 DCs process and present antigens to T cells, stimulate cytotoxicity of NK cells and initiate the adaptive immune response. 15 Studies of the microenvironment in uVIN revealed that ...

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mentioning

confidence: 56%

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Esch

Poelgeest

Trimbos

et al. 2014

Intl Journal of Cancer

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“…CD163 plays a role in preventing tissue inflammation by clearing hemoglobin/ haptoglobin complexes and inducing antioxidative enzyme heme oxygenase-1 [28]. The soluble form of CD163 plays a role in preventing inflammation by preventing T cell activation [28,29]. Thus, high expression of CD163 by M2c macrophages highlights their role in preventing tissue inflammation.…”

Section: Discussionmentioning

confidence: 99%

Characterization of In vitro Generated Human Polarized Macrophages

Iqbal¹,

Kumar²

2015

J Clin Cell Immunol

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“…33 There was a good, but not perfect, correlation between the total number of CD163 þ macrophages and that of hemophagocytic cells identified by hematoxylin-eosin staining (Spearman r ¼ 0.70, Po0.01), which could be explained by the fact that hemophagocytic macrophages identified by hematoxylin-eosin staining are a sub-population of CD163 þ macrophages. [34][35][36] Although an increased number of CD163 þ macrophages was not a statistically significant factor for NRM (adjusted HR 2.1; 95% CI, 0.85-5.0; P ¼ 0.11), limited statistical power precluded us from excluding a clinically meaningful effect of it. Further studies are warranted.…”

Section: Tablementioning

confidence: 98%

Clinical significance of hemophagocytosis in BM clot sections during the peri-engraftment period following allogeneic hematopoietic SCT

Imahashi¹,

Inamoto²,

Ito³

et al. 2011

Bone Marrow Transplant

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The effects of macrophage activation on the outcome of allogeneic hematopoietic SCT (allo-HSCT) have yet to be fully examined. A total of 70 adult patients who received a first allo-HSCT for hematological diseases were studied. We counted the number of hemophagocytic cells in BM clot sections on day þ 14±7, and analyzed its impact on subsequent outcome. In all, 23 patients were diagnosed as having increased numbers of hemophagocytic cells (HP group), whereas 47 were not (non-HP group). The HP group was not associated with an increased incidence of acute or chronic GVHD, but was associated with worse hematopoietic recovery than the non-HP group. The 2-year OS for the HP group and the non-HP group was 30 and 65% (Po0.01), respectively, and 2-year nonrelapse mortality was 48% and 27% (Po0.01), respectively. Multivariate analysis confirmed that the HP group was associated with a lower OS (hazard ratio (HR) ¼ 2.3; 95% confidence interval (CI), 1.0-5.4; P ¼ 0.048) and higher non-relapse mortality (HR ¼ 4.0; 95% CI, 1.6-9.9; Po0.01). The HP group had higher incidences of death due to graft failure (Po0.01) and endothelial complications, such as sinusoidal obstruction syndrome and transplant-associated microangiopathy (P ¼ 0.01). Macrophage activation is a previously unrecognized complication with negative impact on outcome of allo-HSCT.

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Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy

Cited by 308 publications

References 146 publications

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Characterization of In vitro Generated Human Polarized Macrophages

Clinical significance of hemophagocytosis in BM clot sections during the peri-engraftment period following allogeneic hematopoietic SCT

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