Correlation of production of IL-17 with immune suppression relating myeloid-derived suppressor cells (MDSC) and nutritional damages in patients with digestive system cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 437-437
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Takashi Yazawa ◽  
Rei Yashima ◽  
Takashi Kimura ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Immune Suppression ◽  
Th17 Cells ◽  
Digestive System ◽  
Suppressor Cells ◽  
Digestive Cancer ◽  
Cellular Mechanisms ◽  
Neutrophil Lymphocyte Ratio ◽  
Cell Mediated Immune Response ◽  
Inflammatory Bowel

437 Background: Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cellular mechanisms mediating this relationship remain unclear. Th17 cells, which produce the proinflammatory cytokine IL-17, have been recognized as one of the key factors in regulation of inflammatory bowel disease and rheumatoid arthritis. Methods: This study demonstrated that, in patients with digestive system cancers including 7 patients with esophageal, 14 with gastric, 20 with colorectal, 5 with hepatocellular, 7 with cholangiocellular, and 7 with pancreatic carcinomas, IL-17 production was correlated with MDSC level and with markers for nutritional impairment, immune suppression and chronic inflammation. Results: IL-17 production was significantly higher in patients with all types of digestive cancer than in normal volunteers. In addition, IL-17 production levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio, and significantly inversely correlated with cell mediated immune response indicators (lymphocyte PHA-blastogenesis and IL-12 production) and patients’ nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. Conclusions: These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism for disease progression through enhancement of immune suppression or cachexia. Controlling activation of Th17 cells may prove to be a valuable strategy for treatment of patients with gastrointestinal cancer.

Correlation of IL-17 with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 83-83 ◽  
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Daisuke Ujiie ◽  
Mai Ashizawa ◽  
Tomohiro Kikuchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Retinol Binding Protein ◽  
Reactive Protein ◽  
Th 17 ◽  
Cell Mediated Immune Response ◽  
Inflammatory Processes ◽  
Advanced Stages

83 Background: Although a causal relationship linking inflammation and cancer immunity is more widely accepted today, precise cell mechanisms mediating this relationship have not been elucidated. IL-17, a pro-inflammatory cytokine primarily secreted by T helper (Th)17 cells, has previously been associated with inflammatory processes in autoimmune disease. The presence of IL-17 and Th17 cells has been confirmed in various invasive cancers and recently linked to immunosuppression in cancer patients. We investigated systemic inflammation, immune suppression, malnutrition, and prognosis associated with IL-17 in patients with gastric and colorectal cancer. Methods: We measured IL-17 in 106 patients, including 43 with gastric and 63 with colorectal cancer, Production of IL-17 stimulated by PHA was measured by ELISA. MDSC (myeloid-derived suppressor cells), which significantly contribute to immunosuppression, were measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and the SI (stimulation index) of lymphocytes’ blastogenic response were used as markers of cell-mediated immune response. Results: Production of IL-17 increased in advanced stages of gastric and colorectal cancer. IL-17 positively correlated with levels of MDSC, serum concentrations of VEGF, NLR, and levels of CRP, and was inversely correlated with IL-12 production, SI, and nutritional markers including prealbumin and retinol binding protein. Patient cohorts were divided into two groups with IL-17 level (540 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer both significantly worse in patients with high production of IL-17 than in those with low IL-17, although the differences were not significant in patients at stages I and II. Conclusions: The present study suggests that IL-17 may reflect an inflammatory impact on the advancement and progression of cancer, and it may serve as useful marker of immune suppression involving MDSC, malnutrition, and poor prognosis in patients with gastric and colorectal cancer.

Abstract P159: Th17 Cells Are Indispensable for Cardiac Inflammation in Autoimmune Myocarditis

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Tomomi Yamashita ◽  
Hiroyuki Nakayama ◽  
Yasushi Fujio
Keyword(s):  
Chronic Inflammation ◽  
Disease Severity ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Chronic Inflammatory Disease ◽  
Orphan Nuclear Receptor ◽  
Cellular Mechanisms ◽  
Autoimmune Myocarditis ◽  
Inflammatory Reactions ◽  
Cardiac Inflammation

Background: Chronic inflammation is closely associated with heart failure; however, the molecular and cellular mechanisms of inflammatory reactions remain to be fully elucidated. Interleukin(IL)-17 is a pro-inflammatory cytokine that is produced by Th17 cells. Th17 cells are induced by IL-6 and transforming growth factor(TGF-β), through up-regulation of its specific transcriptional factor, retinoic acid receptor-related orphan nuclear receptor(ROR)γt. Th17 cells are reported to participate in pathogenesis of chronic inflammatory disease. In this study, we examined the functional roles of Th17 signaling in cardiac inflammation using murine experimental autoimmune myocarditis(EAM) model. Methods and Results: EAM was induced in wild-type(WT) and/or RORγt-eGFP knock-in Balb/c mice by immunization twice with α-myosin heavy chain peptide. Three weeks after the first immunization, the mRNA expression of RORγt was up-regulated and correlated with the disease severity in heart. Additionally, in immunostaining and flow cytometry analysis, we observed a significant number of Th17 cells among inflammatory cells infiltrating myocardium from WT and RORγt-eGFP knock-in heterozygous mice. These data showed that Th17 cells were remarkably recruited in EAM heart. Moreover, depression of Th17 differentiation suppressed disease severity completely with inhibition of RORγt and IL-17 transcriptional activity, whereas IL-17 neutralizing antibody to lesser extent. Finally, RORγt-eGFP knock-in homozygous mice were protected from cardiac inflammation. Conclusion: Our results indicated that Th17 activation through RORγt pathway is a critical mechanism for the development of myocarditis. However, IL-17 is not crucial for induction of EAM, suggesting that other Th17 producing pro-inflammatory cytokines are involved. It could be proposed that Th17 cells are novel therapeutic target against chronic inflammation in heart.

scholarly journals COVID-19—from mucosal immunology to IBD patients

2021 ◽  
Author(s):  
Carl Weidinger ◽  
Ahmed Nabil Hegazy ◽  
Rainer Glauben ◽  
Britta Siegmund
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Immune Suppression ◽  
Bowel Disease ◽  
Digestive System ◽  
Viral Infections ◽  
Intestinal Epithelial Cells ◽  
Mucosal Immunology ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

AbstractViral infections with SARS-CoV-2 can cause a multi-facetted disease, which is not only characterized by pneumonia and overwhelming systemic inflammatory immune responses, but which can also directly affect the digestive system and infect intestinal epithelial cells. Here, we review the current understanding of intestinal tropism of SARS-CoV-2 infection, its impact on mucosal function and immunology and summarize the effect of immune-suppression in patients with inflammatory bowel disease (IBD) on disease outcome of COVID-19 and discuss IBD-relevant implications for the clinical management of SARS-CoV-2 infected individuals.

Correlation of VEGF with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Daisuke Ujiie ◽  
Mai Ashizawa ◽  
Hirokazu Okayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Serum Levels ◽  
Retinol Binding Protein ◽  
Vascular Permeability Factor ◽  
Reactive Protein ◽  
Cell Mediated Immune Response ◽  
Immunosuppressive Cells

582 Background: Although a causal relationship for inflammation and immunity of cancer is more widely accepted today, the precise cell mechanisms mediating this relationship have not been elucidated. Vascular endothelial growth factor (VEGF), previously known as vascular permeability factor. 45 kDa protein, belongs to a family of platelet-derived growth factors. VEGF, inflammation-related protein, could contribute to the accumulation of immunosuppressive cells (MDSC, Treg, TAM, and Tie-2-expressingmonocytes) in tumor-bearing hosts through direct or indirect mechanisms. Methods: We tested the serum levels of VEGF by ELISA in 106 patients including 43 with gastric and 63 with colorectal cancer, and they were increased in advanced stages of gastric and colorectal cancer. Production of IL-17, pro-inflammatory cytokine, with a stimulation of PHA was measured by ELISA and MDSC (myeloid-derived suppressor cells), one of major immunosuppressing cells, was measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and SI (stimulation index) of blastogenic response of lymphocytes were used as markers of cell-mediated immune response. Results: The concentrations of VEGF were positively correlated with levels of MDSC, production of IL-17, NLR and CRP, and were inversely correlated with IL-12 production, SI and nutritional markers including prealbumin and retinol binding protein. The patients were both divided into two groups with a serum level of VEGF (330 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer were both significantly worse in patients with high levels of VEGF than in those with low VEGF although the differences were not significant in patients with stagesⅠand II. Conclusions: The results of the present study suggested that VEGF may have an impact on advancement and progression involving inflammation and serve as useful markers of the immune suppression involving MDSC, malnutrition and poor prognosis in patients with gastric and colorectal cancer.

scholarly journals Dichotomy between the induction of suppressor cells and immunologic tolerance by adult thymectomy.

1980 ◽  
Vol 151 (3) ◽  
pp. 743-748 ◽  
Author(s):  
Y Borel ◽  
L Kilham ◽  
S E Kurtz ◽  
C L Reinisch
Keyword(s):  
T Cells ◽  
Immune Tolerance ◽  
Immune Suppression ◽  
Antigenic Determinant ◽  
Suppressor Cells ◽  
Immunologic Tolerance ◽  
Suppressor T Cells ◽  
Cellular Mechanisms

Adult thymectomy prevents the development of suppressor T cells without impairing the induction of immunologic tolerance to the same antigenic determinant. This finding demonstrates that the cellular mechanisms underlying immune suppression and immune tolerance are different.

Curative Ayurvedic approach to Ulcerative colitis - A Case Report

2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Dr. Sumedh Wasnik ◽  
Anita Ghodke ◽  
Vaibhav Sulakhe
Keyword(s):  
Ulcerative Colitis ◽  
Weight Loss ◽  
Immune Suppression ◽  
Inflammatory Bowel Diseases ◽  
Life Style ◽  
Intravenous Fluids ◽  
Genetic Origin ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Difficult Issue

Westernization and today’s changing life style is resulting in various health problems like Inflammatory Bowel diseases, which is a common entity encountered in surgical practise. Ulcerative colitis is the most common among them. Though it is believed to have auto immune and genetic origin, today’s life style, environment, diet and stress plays an important role in aetiology. The disease is prevalent in middle aged western and northern people characterised by abdominal pain with bloody diarrhoea, weight loss, anaemia and general debility. This condition has remissions and exacerbations. One should always keep in mind that inflammatory bowel diseases can have anorectal manifestations. Diagnosis is made on the basis of symptoms, stool exam. and endoscopy. Management is symptomatic i.e. antibiotics, anti-inflammatory, anti-spasmodic, multivitamins, immune suppression and if required admission, intravenous fluids. if no response colectomy. As such there is no satisfactory treatment till date, so it remains the difficult issue. Here we need to have an alternative, safe, convenient treatment. Ayurveda has an answer for such cases.

scholarly journals Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1627 ◽  
Author(s):  
Anita Thyagarajan ◽  
Mamdouh Salman A. Alshehri ◽  
Kelly L.R. Miller ◽  
Catherine M. Sherwin ◽  
Jeffrey B. Travers ◽  
...  
Keyword(s):  
Survival Rates ◽  
Suppressor Cells ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Resistance ◽  
Cellular Mechanisms ◽  
Immunosuppressive Cell

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC.

scholarly journals Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging

2021 ◽  
Vol 22 (5) ◽  
pp. 2238
Author(s):  
Nao Nagai ◽  
Yotaro Kudo ◽  
Daisuke Aki ◽  
Hayato Nakagawa ◽  
Koji Taniguchi
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Antitumor Immunity ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Cytotoxic T Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Age Related ◽  
Immunosuppressive Tumor Microenvironment ◽  
Pro Inflammatory Cytokines

Chronic inflammation is thought to promote tumorigenesis and metastasis by several mechanisms, such as affecting tumor cells directly, establishing a tumor-supporting microenvironment, enhancing tumor angiogenesis, and suppressing antitumor immunity. In this review, we discuss the recent advances in our understanding of how inflammation induces the immunosuppressive tumor microenvironment, such as increasing the level of pro-inflammatory cytokines, chemokines, and immunosuppressive molecules, inducing immune checkpoint molecules and cytotoxic T-cell exhaustion, and accumulating regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). The suppression of antitumor immunity by inflammation is especially examined in the liver and colorectal cancer. In addition, chronic inflammation is induced during aging and causes age-related diseases, including cancer, by affecting immunity. Therefore, we also discuss the age-related diseases regulated by inflammation, especially in the liver and colon.

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