Publications
434 results found
Malietzis G, Lee GH, Knight SC, et al., 2015, The Prognostic Significance of CCR7-Positive Cells and Relationship with Body Composition in Colorectal Cancer, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: 60-60, ISSN: 0007-1323
Landy J, Walker AW, Li JV, et al., 2015, Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis, Scientific Reports, Vol: 5, ISSN: 2045-2322
Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and 1H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a “healthier” pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.
Malietzis G, Lee GH, Bernardo D, et al., 2015, The prognostic significance and relationship with body composition of CCR7-positive cells in colorectal cancer, Journal of Surgical Oncology, Vol: 112, Pages: 86-92, ISSN: 1096-9098
Background and ObjectivesThe host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival.MethodsA study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used.ResultsHigh CCR7+ cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7+ cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51–31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24–12.9); P = 0.02 for DFS).ConclusionsOur results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker.
Malietzis G, Lee GH, Bernardo D, et al., 2015, THE RELATIONSHIP WITH BODY COMPOSITION OF CCR7-POSITIVE CELLS IN COLORECTAL CANCER, 2nd Digestive-Disorders-Federation Conference, Publisher: BMJ PUBLISHING GROUP, Pages: A350-A351, ISSN: 0017-5749
Yassin NA, Al-Hassi H, Ansari T, et al., 2015, WHY DO CROHN'S AND IDIOPATHIC ANAL FISTULAE PERSIST?, 2nd Digestive-Disorders-Federation Conference, Publisher: BMJ PUBLISHING GROUP, Pages: A151-A151, ISSN: 0017-5749
Hevia A, Bernardo D, Montalvillo E, et al., 2015, Human colon-derived soluble factors modulate gut microbiota composition, FRONTIERS IN ONCOLOGY, Vol: 5, ISSN: 2234-943X
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- Citations: 4
Ortiz ML, Kumar V, Martner A, et al., 2015, Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17-producing CD4<SUP>+</SUP> T cells, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 212, Pages: 351-367, ISSN: 0022-1007
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- Citations: 62
Mann ER, Bernardo D, English NR, et al., 2015, Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum, Gut, Vol: 65, Pages: 256-270, ISSN: 1468-3288
Objective Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC.Design Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction.Results A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1β) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4+FoxP3+IL-10+ (regulatory) T cells. There were enhanced proportions of CD103+Sirpα− DC in the colon, with increased proportions of CD103+Sirpα+ DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103+Sirpα+ DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103+ DC, in particular CD103+Sirpα+ DC. However, expression of ILT3 was associated with CD103− DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells.Conclusions The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting.
Moret-Tatay I, Siaw YH, Man R, et al., 2015, Characterization of human colonic and ileal dendritic cells in health and Crohn's disease, JOURNAL OF CROHNS & COLITIS, Vol: 9, Pages: S79-S79, ISSN: 1873-9946
Yassin NA, Hendy P, Horder C, et al., 2015, The Gut Microbiome-Immune System Interaction as an Aetiological Factor for Fistulising Perianal Crohn's Disease, JOURNAL OF CROHNS & COLITIS, Vol: 9, Pages: S81-S82, ISSN: 1873-9946
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- Citations: 2
Al-Hassi H, Vora R, Durga R, et al., 2015, Adipokines link childhood Crohn's disease and the gut immune system., JOURNAL OF CROHNS & COLITIS, Vol: 9, Pages: S84-S85, ISSN: 1873-9946
Vora R, Bernardo D, Fell J, et al., 2015, Abnormal gut homing and activation profile of blood and colonic dendritic cells in paediatric Crohn's disease normalises in response to nutritional therapy, JOURNAL OF CROHNS & COLITIS, Vol: 9, Pages: S68-S68, ISSN: 1873-9946
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- Citations: 1
Daulatzai N, Hart AL, Phillips RKS, et al., 2015, The Role of Dendritic and T-Cell Function and Migration in the Development of Cutaneous Wound Failure in Crohn's Disease, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY-BLACKWELL, Pages: 166-166, ISSN: 0007-1323
Hendy PA, Bernardo D, Al-Hassi HO, et al., 2015, PTH-057 Dendritic cell phenotype in crohn’s disease may correlate with disease severity and explain the high prevalence of cutaneous manifestations, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology, Pages: A430-A431
Malietzis G, Lee GH, Jenkins JT, et al., 2015, Prognostic Value of the Tumour-Infiltrating Dendritic Cells in Colorectal Cancer: A Systematic Review, CELL COMMUNICATION AND ADHESION, Vol: 22, Pages: 9-14, ISSN: 1541-9061
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- Citations: 12
Mann ER, Bernardo D, Ng SC, et al., 2014, Human Gut Dendritic Cells Drive Aberrant Gut-specific T-cell Responses in Ulcerative Colitis, Characterized by Increased IL-4 Production and Loss of IL-22 and IFNγ, INFLAMMATORY BOWEL DISEASES, Vol: 20, Pages: 2299-2307, ISSN: 1078-0998
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- Citations: 43
Thompson IJT, Mann ER, Stokes MG, et al., 2014, Specific activation of dendritic cells enhances clearance of bacillus anthracis following infection, PLoS One, Vol: 9, Pages: 1-9, ISSN: 1932-6203
Dendritic cells are potent activators of the immune system and have a key role in linking innate and adaptive immune responses. In the current study we have used ex vivo pulsed bone marrow dendritic cells (BMDC) in a novel adoptive transfer strategy to protect against challenge with Bacillus anthracis, in a murine model. Pre-pulsing murine BMDC with either recombinant Protective Antigen (PA) or CpG significantly upregulated expression of the activation markers CD40, CD80, CD86 and MHC-II. Passive transfusion of mice with pulsed BMDC, concurrently with active immunisation with rPA in alum, significantly enhanced (p<0.001) PA-specific splenocyte responses seven days post-immunisation. Parallel studies using ex vivo DCs expanded from human peripheral blood and activated under the same conditions as the murine DC, demonstrated that human DCs had a PA dose-related significant increase in the markers CD40, CD80 and CCR7 and that the increases in CD40 and CD80 were maintained when the other activating components, CpG and HK B. anthracis were added to the rPA in culture. Mice vaccinated on a single occasion intra-muscularly with rPA and alum and concurrently transfused intra-dermally with pulsed BMDC, demonstrated 100% survival following lethal B. anthracis challenge and had significantly enhanced (p<0.05) bacterial clearance within 2 days, compared with mice vaccinated with rPA and alum alone.
Landy J, Al-Hassi HO, Ronde E, et al., 2014, Innate Immune Factors in the Development and Maintenance of Pouchitis, INFLAMMATORY BOWEL DISEASES, Vol: 20, Pages: 1942-1949, ISSN: 1078-0998
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- Citations: 10
Bernardo D, Montalvillo E, Bassity E, et al., 2014, Dendritic cell compartmentalization through the human colon, 9th European-Mucosal-Immunology-Group Meeting, Publisher: WILEY-BLACKWELL, Pages: 6-7, ISSN: 0019-2805
Lee G, Malietzis G, Bernardo D, et al., 2014, Circulating dendritic cells are gut homing in colorectal cancers - A role in diagnosis and prognosis in colorectal cancer?, EUROPEAN JOURNAL OF CANCER, Vol: 50, Pages: S217-S217, ISSN: 0959-8049
Malietzis G, Lee GH, Bernardo D, et al., 2014, Muscle mass of the host and dendritic cell phenotype in patients with colorectal cancer, EUROPEAN JOURNAL OF CANCER, Vol: 50, Pages: S218-S218, ISSN: 0959-8049
Lee G, Malietzis G, Bernardo D, et al., 2014, Activation and homing profile of dendritic cells in human colorectal cancer - effect of tumour derived factors or leaky lymph nodes?, EUROPEAN JOURNAL OF CANCER, Vol: 50, Pages: S217-S217, ISSN: 0959-8049
Condamine T, Kumar V, Ramachandran I, et al., 2014, ER stress response regulates the fate of myeloid-derived suppressor cells through TRAIL receptors mediated apoptosis, JOURNAL OF IMMUNOLOGY, Vol: 192, ISSN: 0022-1767
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- Citations: 1
Condamine T, Kumar V, Ramachandran IR, et al., 2014, ER stress regulates myeloid-derived suppressor cell fate through TRAIL-R–mediated apoptosis, Journal of Clinical Investigation, Vol: 124, Pages: 2626-2639, ISSN: 1558-8238
Yassin NA, Siaw YH, Bernardo D, et al., 2014, Expression of gut homing molecules on perianal Crohn's fistulae, Annual Meeting of the Society-of-Academic-and-Research-Surgery, Publisher: WILEY-BLACKWELL, Pages: 2-2, ISSN: 0007-1323
Al-Hassi HO, Mann ER, Sanchez B, et al., 2014, Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp, MOLECULAR NUTRITION & FOOD RESEARCH, Vol: 58, Pages: 1132-1143, ISSN: 1613-4125
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- Citations: 49
Vora R, Bernardo D, Fell J, et al., 2014, Effect of enteral nutrition on dendritic cell phenotype in children with Crohn's disease, JOURNAL OF CROHNS & COLITIS, Vol: 8, Pages: S95-S95, ISSN: 1873-9946
Yassin NA, Askari A, Siaw YH, et al., 2014, Gut homing markers in perianal Crohn's fistulae, JOURNAL OF CROHNS & COLITIS, Vol: 8, Pages: S9-S9, ISSN: 1873-9946
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- Citations: 1
You J, Dong H, Mann ER, et al., 2014, Probiotic modulation of dendritic cell function is influenced by ageing, IMMUNOBIOLOGY, Vol: 219, Pages: 138-148, ISSN: 0171-2985
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- Citations: 33
Comino I, Suligoj T, Al-Hassi HO, et al., 2014, Constitutive gut-homing capacity on circulating myeloid dendritic cells in coeliac disease, REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS, Vol: 106, Pages: 64-65, ISSN: 1130-0108
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