Recruitment of dendritic cells in human liver with metastases

Gulubova, Maya; Manolova, Irena; Cirovski, G.; Sivrev, D.

doi:10.1007/s10585-008-9191-1

Cited by 14 publications

(6 citation statements)

References 25 publications

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“…(26) and Smad7 (15,25), may participate in the state of apparent immunologic hyporesponsiveness displayed by the decrease in DC number in the tumor microenvironment. Unlike others (27), we have found previously, the presence of CD1a + and CD83 + DCs in normal liver sinusoids (28). Immunohistochemically, we also found an increased number of CD1a + and CD83 + DCs and an increased percentage of CD83 + DCs by flow cytometry in the liver sinusoids and portal tracts surrounding metastasis as compared with the remote liver tissue.…”

Section: Metastasescontrasting

confidence: 55%

Relationship of TGF‐β1 and Smad7 expression with decreased dendritic cell infiltration in liver gastrointestinal cancer metastasis

Gulubova

Manolova

Ananiev

et al. 2013

APMIS

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Immune responses and their modulation within the liver are critical to the outcome of liver malignancies. In late-stage tumors, secreted TGF-β promotes oncogenic functions and can confer tolerogenicity to some immune cells like DCs. The TGF-β signaling pathway is involved in the control of several biological processes, including immunosurveillance. The aim of the present study was to assess CD1a(+) and CD83(+) DCs and to evaluate the impact of TGF-β pathway on DCs maturation and distribution in the liver metastases from gastric and colorectal tumors. The percentage of CD83(+) DCs in the liver tissue, surrounding metastasis and in the metastasis-free liver was measured by flow cytometry, and TGF-β levels were assessed in the tissue supernatant from the peritumoral liver after mononuclear cell isolation and in the sera of the same patients. CD1a(+) and CD83(+) DCs were observed in the tumor stroma and border. Out of 73 patients, there was cytoplasmic reactivity: of TGF-β1 in 37 (50.7%); of Smad4 in 62 (84.9%); of Smad7 in 46 (63%), and of TGFβRII in 39 (53.4%) of the metastases. The TGF-β1 expression in tumor cell cytoplasm correlated with low CD1a(+) and low CD83(+) DCs infiltration. The tissue levels of TGF-β1, measured by ELISA in the supernatant were significantly increased in metastases than in normal liver. Using a two-color FACS analysis, we found that the percentage of HLA-DR(+) CD83(+) DCs in metastases was significantly decreased as compared with metastasis-free liver tissue. In conclusion, the positive and negative correlations between the mediators from the TGF-β pathway implied the existence of imbalance and suppression of this cytokine activity. The presence of increased TGF-β expression by immunohistochemistry in tumor cells was confirmed by detection of increased TGF-β tissue level in the supernatant from the tissue homogenate. The observation of low numbers of CD1a(+) and CD83(+) DCs in tumor stroma correlated with TGF-β overexpression in tumor cells, a fact that well documents the immunosuppressive role of TGF-β in metastasis development. The increased percentage of CD83(+) DCs in the peritumoral tissue supposes that there could be active recruitment or local differentiation of DCs in the metastasis border, but inside the tumor the immune cells recruitment and activity are suppressed by TGF-β and by other cytokines.

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Section: Metastasescontrasting

confidence: 55%

Relationship of TGF‐β1 and Smad7 expression with decreased dendritic cell infiltration in liver gastrointestinal cancer metastasis

Gulubova

Manolova

Ananiev

et al. 2013

APMIS

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“…Gulubova et al. () reported that S‐100 protein‐positive cells were more than CD83‐, and CD1‐positive cells in tumour tissue and portal tracts of metastatic and normal human liver tissue. Similarly to last authors, we also could suggest a significance of the paranal sinus dendritic cells in the development of host immune defence mechanisms, including anti‐tumour immunity like in the liver.…”

Section: Discussionmentioning

confidence: 99%

S‐100 Protein‐Positive Mast Cells in Canine Paranal Sinus (Sinus paranalis)

Stefanov

Vodenicharov

2013

Anat Histol Embryol

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The aim of this study was to establish the immunocytochemical expression of S-100 protein in mast cells, localized in the wall of dog's paranal sinus. Control serial sections were used for immunocytochemical detection of tryptase-positive mast cells. It was observed that S-100-positive cells have the same morphology and localization as the tryptase-positive mast cells, which indicated that S-100-positive cells are most probably mast cells with abilities as dendritic cells. In conclusion, for the first time, the current study gave evidence that mast cells in this organ possess one more function, such as dendritic cells.

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“…The exact mechanism of this phenomenon is unknown. Recruitment of various populations of phagocytic cells (monocytes, macrophages, and dendritic cells) of the RES is involved in the immune response against tumor cell deposits in liver 39 , 40 . Since liposomes are mainly cleared by RES and liver is an important functional center of RES, the increased clearance of encapsulated CKD‐602 may be due to enhanced RES activity in patients with liver tumor.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Pegylated Liposomal CKD‐602 (S‐CKD602) in Patients With Advanced Malignancies

Ramanathan

Zamboni

et al. 2012

The Journal of Clinical Pharma

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S-CKD602 is a pegylated long-circulating liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. A population pharmacokinetic (PK) model for encapsulated and released CKD-602 following administration of S-CKD602 was developed to assess factors that may influence S-CKD602 PK. Plasma samples from 45 patients with solid tumors were collected in a phase 1 study. S-CKD602 was administered as a 1-hour intravenous infusion with doses ranging from 0.1 to 2.5 mg/m(2) . Plasma concentrations of encapsulated and released CKD-602 were used to develop a population PK model using NONMEM. PK of encapsulated CKD-602 was described by a 1-compartment model with nonlinear clearance, and PK of released CKD-602 was described by a 2-compartment model with linear clearance for all patients. Covariate analysis revealed that tumor in the liver was a significant covariate for clearance of encapsulated CKD-602 and that age significantly influenced the release rate of CKD-602 from S-CKD602. Maximum elimination rate in patients with liver tumor is 1.5-fold higher compared with patients without liver tumor. Release rate of CKD-602 from S-CKD602 in patients less than 60 years old was 2.7-fold higher compared with patients 60 years old or older. These observations have potential implications in the optimal dosing of liposomal agents.

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Recruitment of dendritic cells in human liver with metastases

Cited by 14 publications

References 25 publications

Relationship of TGF‐β1 and Smad7 expression with decreased dendritic cell infiltration in liver gastrointestinal cancer metastasis

Relationship of TGF‐β1 and Smad7 expression with decreased dendritic cell infiltration in liver gastrointestinal cancer metastasis

S‐100 Protein‐Positive Mast Cells in Canine Paranal Sinus (Sinus paranalis)

Population Pharmacokinetics of Pegylated Liposomal CKD‐602 (S‐CKD602) in Patients With Advanced Malignancies

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