Tumor microenvironment converts plasmacytoid dendritic cells into immunosuppressive/tolerogenic cells: insight into the molecular mechanisms
Demoulin, Stéphanie ; Herfs, Michael ; Delvenne, Philippe et al
in Journal of Leukocyte Biology (2013), 93(3), 343-352
Human pDCs represent a rare population of circulating cells characterized by a rapid and massive TLR-dependent secretion of type I IFN in response to pathogenic agents or danger signals. Through their ... [more ▼]
Human pDCs represent a rare population of circulating cells characterized by a rapid and massive TLR-dependent secretion of type I IFN in response to pathogenic agents or danger signals. Through their capacity to bring together innate and adaptive immunity and to secrete soluble factors controlling cancer development, these cells could represent important actors in antitumor immunity. However, accumulating evidence suggests that pDCs recruited to the tumor microenvironment often display a nonactivated state and are associated with the development and maintenance of immunosuppression. Here, we present an overview of neoplastic lesions associated with an infiltration of immunosuppressive/ tolerogenic pDC. Moreover, as the proper response of pDC against cancer depends on a critical balance between immune-activating and immune-suppressing mechanisms, we summarize current knowledge about the molecular pathways developed by tumors to prevent antitumoral pDC immune responses. A better understanding of the mechanisms regulating pDC function in tumors could aid in the development of new therapies. Indeed, effective cancer vaccines or therapies could combine immunoactivating strategies (i.e., TLR agonists) with elimination of immune-suppressing mechanisms, leading to pDC reprogramming and thus, allowing tumor rejection in a clinical setting. [less ▲]Detailed reference viewed: 56 (15 ULg)
Role of Gamma Delta T cells in HPV-induced Cancer Progression
Van hede, Dorien ; ; et al
Poster (2013, January 28)Detailed reference viewed: 40 (11 ULg)
Novel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.
EL SHAZLY, Amr ; Begon, Dominique ; KUSTERMANS, Gaëlle et al
in Journal of Biological Chemistry (2013), 288(2), 1374-84
We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and ... [more ▼]
We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues, showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase inhibition, or calcium chelation. Western blot demonstrated a novel CRTH2 mediated cytosol to membrane translocation of PKC-epsilon, PKC-delta and PKA-alpha, gamma and IIalpha reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. [less ▲]Detailed reference viewed: 31 (6 ULg)
Organized Proteomic Heterogeneity in Colorectal Cancer Liver Metastases and Implications for Therapies
Turtoi, Andrei ; ; et al
in Hepatology (Baltimore, Md.) (2013)
Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems ... [more ▼]
Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis dis- played increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demon- strate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of target- able antigens. [less ▲]Detailed reference viewed: 18 (7 ULg)
Cutaneous melanocytomas: a conceptual cluster of atypical and indolent melanocytic neoplasms.
PIERARD, Gérald ; FRANCHIMONT, Claudine ; HERMANNS, Trinh et al
in Expert Review of Dermatology (2013), 8Detailed reference viewed: 3 (1 ULg)
Immunohistochemical sweat gland profiles.
; Pierard, Gérald ; Delvenne, Philippe et al
in Journal of Cosmetic Dermatology (2013), 12
Abstract BACKGROUND: Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. AIMS: Some immunohistochemical markers ... [more ▼]
Abstract BACKGROUND: Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. AIMS: Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. METHODS: This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. RESULTS: The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. CONCLUSION: Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. [less ▲]Detailed reference viewed: 9 (2 ULg)
Dendritic cells in Barrett's esophagus carcinogenesis: an inadequate microenvironment for antitumor immunity?
Somja, Joan ; Demoulin, Stéphanie ; RONCARATI, Patrick et al
in American Journal of Pathology (2013)Detailed reference viewed: 47 (12 ULg)
18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture.
Courtois, Audrey ; Richelle, Betty ; Hustinx, Roland et al
in Journal of Nuclear Medicine (The) (2013)
Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots of positive uptake of ... [more ▼]
Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots of positive uptake of 18F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the 18F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no 18F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. METHODS: Biopsies of the AAA wall were obtained from patients with no 18F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site of positive uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. RESULTS: The sites of the aneurysmal wall with a positive 18F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. CONCLUSION: Positive 18F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture. [less ▲]Detailed reference viewed: 57 (26 ULg)
Novel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue
EL SHAZLY, Amr ; ; et al
Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed ... [more ▼]
Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy. Objective: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. Methods: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. Results: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. Conclusions and Clinical Relevance: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway. [less ▲]Detailed reference viewed: 8 (0 ULg)
Expansion of CD16+ CD56+ NK cells in vericyte® NK cell growth medium
Brohée, Laura ; Bastin, Renaud ; et al
Natural Killer (NK) cells play a key role in host resistance to virus and tumour. These cells are potent killers of virus infected and tumour cells via a direct recognition of the target by activation ... [more ▼]
Natural Killer (NK) cells play a key role in host resistance to virus and tumour. These cells are potent killers of virus infected and tumour cells via a direct recognition of the target by activation receptor such as NKG2D or by inducing Fcγ receptor (FcγRIII, CD16) mediated antibody dependent cellular cytotoxicity (ADCC). Current NK cell-based cancer immunotherapy aims to produce large amounts of functional NK cells, unfortunately most culture media used for NK cell expansion induced the downregulation of CD16 on NK cells. Here, we tested the impact of a new NK cell growth medium (Vericyte® from Medicyte) on CD16 expression. Sorted NK cells and peripheral blood mononuclear cells (PBMC) were cultivated in vericyte® NK cell growth medium and cells issued from these cultures were characterized in term of expansion and phenotype at several time points. After 5 days of culture, an expansion of both NK cells and PBMC was observed and maintained at least until day 20 of culture. In PBMC cultures, we observe only a small preferential NK cell growth since NK cells were around 5-10% at beginning of the culture and this percentage increased to 15% at the end of the culture. However, these cells showed a high proliferative potential when we started the culture with sorted NK cells (the proportion of contaminant cells remain low, under 5%). NK cells expressed CD56 and NKp46 and interestingly after a decreased expression of CD16 on the cell surface at day 3, this receptor was up regulated and most of the cells are CD56bright CD16bright from day 7 to day 12. According FACS FCS/SSC dot plot, NK cells acquired morphology of large activated lymphocytes and some of them expressed activation markers such CD25. Finally, these cells were able to kill efficiently tumour cell line K562. Thus our data show that vericyte® NK cell growth medium allows the expansion of functional CD16+CD56+ NK cells. Cytokine production and ADCC function are under investigation. [less ▲]Detailed reference viewed: 21 (2 ULg)
L'addiction au Soleil, son estocade et la parade des crèmes solaires.
FRANCHIMONT, Claudine ; HERMANNS, Trinh ; PIERARD, Gérald et al
in Revue Médicale de Liège (2013), 68(5-6), 321-325Detailed reference viewed: 10 (0 ULg)
Analytic dermoscopy of superficial basal cell carcinoma.
FRANCHIMONT, Claudine ; ; et al
in Journal of Case Reports in Medicine (2013), 3Detailed reference viewed: 11 (2 ULg)
In vivo evaluation of the skin tensile strength by the suction method: pilot study coping with hysteresis and creep extension.
PIERARD, Gérald ; Pierard, Sébastien ; Delvenne, Philippe et al
in ISRN dermatology (2013), 2013
From an engineering standpoint, both the skin and subcutaneous tissue act as interconnected load-transmitting structures. They are subject to a variety of intrinsic and environmental influences. Changes ... [more ▼]
From an engineering standpoint, both the skin and subcutaneous tissue act as interconnected load-transmitting structures. They are subject to a variety of intrinsic and environmental influences. Changes in the cutaneous viscoelasticity represent an important aspect in a series of skin conditions. The aim of this work was to explore the methodology of biomechanical measurements in order to better appreciate the evolution and severity of some connective tissue diseases. The Cutometer MPA 580 (C+K electronic) was used in the steep and progressive suction procedures. Adapting measurement modalities was explored in order to mitigate any variability in data collection. The repeat steep suction procedure conveniently reveals the creep phenomenon. By contrast, the progressive suction procedure highlights the hysteresis phenomenon. These viscoelastic characteristics are presently described using the 2 and 4 mm probes on normal skin and in scleroderma, acromegaly, corticosteroid-induced dermatoporosis, and Ehlers-Danlos syndrome. The apposition of an additional outer contention on the skin altered differently the manifestations of the creep extension and hysteresis among the tested skin conditions. Any change in the mechanical test procedure affects the data. In clinical and experimental settings, it is mandatory to adhere to a strict and controlled protocol. [less ▲]Detailed reference viewed: 6 (1 ULg)
Dissection of Iliac Artery in a Patient With Autosomal Dominant Polycystic Kidney Disease
Courtois, Audrey ; Nusgens, Betty ; DELVENNE, Philippe et al
in AORTA (2013), 1(2), 123-125Detailed reference viewed: 19 (8 ULg)
Myoferlin is a key regulator of EGFR activity in breast cancer.
Turtoi, Andrei ; Blomme, Arnaud ; Bellahcene, Akeila et al
in Cancer Research (2013)
Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its ... [more ▼]
Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its expression in and contributions to cancer are not well established. In this study, we show that myoferlin is overexpressed in human breast cancers and that it is has a critical role in controlling degradation of the EGFR after its activation and internalization in breast cancer cells. Myoferlin depletion blocked EGF-induced cell migration and epithelial-to-mesenchymal transition. Both effects were induced as a result of impaired degradation of phosphorylated EGFR via dysfunctional plasma membrane caveolae and alteration of caveolin homooligomerization. In parallel, myoferlin depletion reduced tumor development in a chicken chorioallantoic membrane xenograft model of human breast cancer. Considering the therapeutic significance of EGFR targeting, our findings identify myoferlin as an novel candidate function to target for future drug development. [less ▲]Detailed reference viewed: 33 (5 ULg)
Toxic Epidermal Necrolysis and Graft-versus-Host Reaction: Revisiting a Puzzling Similarity.
PIERARD, Gérald ; Hermanns-Lê, Trinh ; PAQUET, Philippe et al
in ISRN Dermatology (2013)Detailed reference viewed: 17 (2 ULg)
Development of anti-HPV lipoplexes for the treatment of cervical cancer
Lechanteur, Anna ; Furst, Tania ; Evrard, Brigitte et al
Poster (2013)Detailed reference viewed: 20 (11 ULg)
The skin landscape in diabetes mellitus. Focus on dermocosmetic management.
PIERARD, Gérald ; ; HERMANNS, Trinh et al
in Clinical, Cosmetic and Investigational Dermatology (2013), 6
BACKGROUND: Some relationships are established between diabetes mellitus (DM) and a series of cutaneous disorders. Specific dermatoses are markers for undiagnosed DM. Other disorders represent supervening ... [more ▼]
BACKGROUND: Some relationships are established between diabetes mellitus (DM) and a series of cutaneous disorders. Specific dermatoses are markers for undiagnosed DM. Other disorders represent supervening complications in an already treated DM patient. OBJECTIVE: To review the information about dermocosmetic care products and their appropriate use in the management and prevention of dermatoses related to DM. METHOD: The peer-reviewed literature and empiric findings are covered. Owing to the limited clinical evidence available for the use of dermocosmetics, a review of the routine practices and common therapies in DM-related dermatoses was conducted. RESULTS: Some DM-related dermatoses (acanthosis nigricans, pigmented purpuric dermatosis) are markers of macrovascular complications. The same disorders and some others (xerosis, Dupuytren's disease) have been found to be more frequently associated with microangiopathy. Other skin diseases (alopecia areata, vitiligo) were found to be markers of autoimmunity, particularly in type 1 DM. Unsurprisingly, using dermocosmetics and appropriate skin care has shown objective improvements of some DM-related dermatoses, such effects improve the quality of life. The most common skin manifestations of DM fall along continuum between "dry skin," xerosis, and acquired ichthyosis, occurring predominately on the shins and feet. Dermocosmetic products improve the feeling of well-being for DM patients. [less ▲]Detailed reference viewed: 14 (0 ULg)
Comment j'explore ... l'atteinte fonctionnelle cutanee d'une sclerodermie.
HERMANNS, Trinh ; Franchimont, Claudine ; PIERARD, Gérald et al
in Revue Médicale de Liège (2013), 68(3), 141-7
Scleroderma refers to distinct clinical presentations sharing in common a sclerotic process most often clinically obvious on the skin. The involvement possibly affects the skin alone in morphea or in ... [more ▼]
Scleroderma refers to distinct clinical presentations sharing in common a sclerotic process most often clinically obvious on the skin. The involvement possibly affects the skin alone in morphea or in combination with internal lesions in systemic sclerosis. Some objective and non-invasive functional assessments are useful for better appreciating the severity and evolution of the disease, as well as to monitor the therapeutic efficacy. In this endeavour, in vivo measurements of the skin mechanical properties are unsurprisingly informative. [less ▲]Detailed reference viewed: 13 (3 ULg)