Epithelial and Immune Cell Responses to Helicobacter pylori That Shape the Gastric Tumor Microenvironment

2021 ◽  
pp. 155-197
Author(s):  
Meaghan Torvund ◽  
Jayati Chakrabarti ◽  
Yana Zavros
Keyword(s):  
Helicobacter Pylori ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Gastric Tumor ◽  
Cell Responses

scholarly journals P2X7 is a cytotoxic receptor….maybe not: implications for cancer

2020 ◽  
Author(s):  
Francesco Di Virgilio
Keyword(s):  
Tumor Microenvironment ◽  
P2x7 Receptor ◽  
Immune Cell ◽  
Extracellular Atp ◽  
P2 Receptors ◽  
Cell Responses ◽  
Experimental Findings ◽  
Cancer Studies

AbstractThe tumor microenvironment is rich in extracellular ATP. This nucleotide affects both cancer and infiltrating immune cell responses by acting at P2 receptors, chiefly P2X7. ATP is then degraded to generate adenosine, a very powerful immunosuppressant. The purinergic hypothesis put forward by Geoff Burnstock prompted innovative investigation in this field and provided the intellectual framework to interpret a myriad of experimental findings. This is a short appraisal of how Geoff’s inspiration influenced cancer studies and my own investigation highlighting the key role of the P2X7 receptor.

scholarly journals Stromal Cells Induce Th17 during Helicobacter pylori Infection and in the Gastric Tumor Microenvironment

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53798 ◽  
Author(s):  
Irina V. Pinchuk ◽  
Katherine T. Morris ◽  
Robert A. Nofchissey ◽  
Rachel B. Earley ◽  
Jeng-Yih Wu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Helicobacter Pylori Infection ◽  
Gastric Tumor

Altered myeloid and lymphoid immune cell responses following repeated social defeat stress

2015 ◽  
Vol 48 (06) ◽  
Author(s):  
O Ambree ◽  
C Ruland ◽  
P Zwanzger ◽  
V Arolt ◽  
J Alferink
Keyword(s):  
Immune Cell ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Cell Responses

scholarly journals Recent Advancements on Immunomodulatory Mechanisms of Resveratrol in Tumor Microenvironment

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1343
Author(s):  
Gagan Chhabra ◽  
Chandra K. Singh ◽  
Deeba Amiri ◽  
Neha Akula ◽  
Nihal Ahmad
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cell ◽  
Cancer Therapies ◽  
Regulatory Cells ◽  
Immunomodulatory Effects ◽  
Cancer Management ◽  
Natural Agents ◽  
Anticancer Effects ◽  
Cancer Types ◽  
Immune Related Genes

Immunomodulation of the tumor microenvironment is emerging as an important area of research for the treatment of cancer patients. Several synthetic and natural agents are being investigated for their ability to enhance the immunogenic responses of immune cells present in the tumor microenvironment to impede tumor cell growth and dissemination. Among them, resveratrol, a stilbenoid found in red grapes and many other natural sources, has been studied extensively. Importantly, resveratrol has been shown to possess activity against various human diseases, including cancer. Mechanistically, resveratrol has been shown to regulate an array of signaling pathways and processes involving oxidative stress, inflammation, apoptosis, and several anticancer effects. Furthermore, recent research suggests that resveratrol can regulate various cellular signaling events including immune cell regulation, cytokines/chemokines secretion, and the expression of several other immune-related genes. In this review, we have summarized recent findings on resveratrol’s effects on immune regulatory cells and associated signaling in various cancer types. Numerous immunomodulatory effects of resveratrol suggest it may be useful in combination with other cancer therapies including immunotherapy for effective cancer management.

scholarly journals ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangming Hou ◽  
Yingjuan Xu ◽  
Dequan Wu
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Protein Protein Interaction ◽  
Oxidative Phosphorylation Pathway ◽  
Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

scholarly journals 492 Integration of high dimensional datasets in an immunocompetent mammary mouse model reveals pathways of tolerance and resistance to immune checkpoint blockade

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A528-A528
Author(s):  
Lin Ma ◽  
Jian-Hua Mao ◽  
Mary Helen Barcellos-Hoff ◽  
Jade Moore
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Systemic Disease ◽  
Ct Imaging ◽  
High Dimensional ◽  
Cytokine Signaling ◽  
Immune Infiltrate ◽  
Pet Ct

BackgroundCheckpoint inhibitors can induce robust and durable responses in a subset of patients. Extending this benefit to more patients could be facilitated by better understanding of how interacts with immune cells with the tumor microenvironment, which is a critical barrier to control both local and systemic disease. The composition and pattern of the immune infiltrate associates with the likelihood of response to immunotherapy. Inflamed tumors that exhibit a brisk immune cell infiltrate are responsive, while those in which immune cells are completely or partially excluded are not. Transforming growth factor β (TGFβ) is immunosuppressive and associated with the immune excluded phenotype.MethodsUsing an immune competent mammary tumor derived transplant (mTDT) model recently developed in our lab, exhibits inflamed, excluded or deserts immune infiltrate phenotypes based on localization of CD8 lymphocytes. Using whole transcriptome deep sequencing, cytof, and PET-CT imaging, we evaluated the tumor, microenvironment, and immune pathway activation among immune infiltrate phenotypes.ResultsThree distinct inflamed tumors phenotypes were identified: ‘classically’ inflamed characterized by pathway evidence of increased CD8+ T cells and decreased PD-L1 expression, inflamed tumors with pathways indicative of neovascularization and STAT3 signaling and reduced T cell mobilization, and an inflamed tumor with increased immunosuppressive myeloid phenotypes. Excluded tumors were characterized by TGFβ gene expression and pro-inflammatory cytokine signaling (e.g. TNFα, IL1β), associated with decreased leukocytes homing and increased immune cell death of cells. We visualized and quantified TGFβ activity using PET-CT imaging of 89Zr-fresolimumab, a TGFβ neutralizing antibody. TGFβ activity was significantly increased in excluded tumors compared to inflamed or desert tumors, which was supported by quantitative pathology (Perkin Elmer) of its canonical signaling target, phosphorylated SMAD2 (pSMAD2). pSMAD2 was positively correlated with PD-L1 expression in the stroma of excluded tumors. In contrast, in inflamed tumors, TGFβ activity positively correlated with increased F4/80 positive macrophages and negatively correlated with expression of PD-L1. CyTOF analysis of tumor and spleen immune phenotypes revealed increased trafficking of myeloid cells in mice bearing inflamed tumors compared to excluded and deserts.ConclusionsThe immunocompetent mTDT provides a model that bridges the gap between the immune landscape and tumor microenvironment. Integration of these high-dimensional data with further studies of response to immunotherapies will help to identify tumor features that favor response to treatment or the means to convert those that are unresponsive.

scholarly journals Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma

2021 ◽  
Author(s):  
Rosanna L. Wustrack ◽  
Evans Shao ◽  
Joey Sheridan ◽  
Melissa Zimel ◽  
Soo-Jin Cho ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Cd8 T Cells ◽  
Tumor Size ◽  
Immune Cell ◽  
Human Cancer ◽  
Soft Tissue Sarcomas ◽  
Inverse Correlation ◽  
Anatomical Location ◽  
Pleomorphic Sarcoma

Abstract Background Soft-tissue sarcomas (STS) are a rare group of mesenchymal malignancies that account for approximately 1% of adult human cancer. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common subtypes of adult STS. Clinical stratification of UPS patients has not evolved for decades and continues to rely on tumor-centric metrics including tumor size and depth. Our understanding of how the tumor microenvironment correlates to these clinicopathologic parameters remains limited. Methods Here, we performed single-cell flow cytometric immune-based profiling of 15 freshly resected UPS tumors and integrated this analysis with clinical, histopathologic, and outcomes data using both a prospective and retrospective cohort of UPS patients. Results We uncovered a correlation between physiologic and anatomic properties of UPS tumors and the composition of immune cells in the tumor microenvironment. Specifically, we identified an inverse correlation between tumor-infiltrating CD8 + T cells and UPS tumor size; and a positive correlation between tumor-infiltrating CD8 + T cells and overall survival. Moreover, we demonstrate an association between anatomical location (deep or superficial) and frequency of CD4 + PD1hi infiltrating T cells in UPS tumors. Conclusions Our study provides an immune-based analysis of the tumor microenvironment in UPS patients and describes the different composition of tumor infiltrating lymphocytes based on size and tumor depth.

scholarly journals The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1346
Author(s):  
Priya Veluswamy ◽  
Max Wacker ◽  
Dimitrios Stavridis ◽  
Thomas Reichel ◽  
Hendrik Schmidt ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Cardiovascular Complications ◽  
World Health ◽  
Endothelial Glycocalyx ◽  
Pathological State ◽  
Mediated Action ◽  
Cell Responses ◽  
Health Organization

The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.

705 Anti-tumor activity of CB-668, a potent, selective and orally bioavailable small-molecule inhibitor of the immuno-suppressive enzyme Interleukin 4 (IL-4)-Induced Gene 1 (IL4I1)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A747-A747
Author(s):  
Andrew MacKinnon ◽  
Deepthi Bhupathi ◽  
Jason Chen ◽  
Tony Huang ◽  
Weiqun Li ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Interleukin 4 ◽  
Mouse Tumor ◽  
Syngeneic Mouse ◽  
Molecule Inhibitor ◽  
Anti Tumor Activity ◽  
Mouse Tumor Models

BackgroundTumors evade destruction by the immune system through multiple mechanisms including altering metabolism in the tumor microenvironment. Metabolic control of immune responses occurs through depletion of essential nutrients or accumulation of toxic metabolites that impair immune cell function and promote tumor growth. The secreted enzyme interleukin 4 (IL-4)-induced gene 1 (IL4I1) is an L-phenylalanine oxidase that catabolizes phenylalanine and produces phenyl-pyruvate and hydrogen peroxide. IL4I1 regulates several aspects of adaptive immunity in mice, including inhibition of cytotoxic T cells through its production of hydrogen peroxide (reviewed in1). In human tumors, IL4I1 expression is significantly elevated relative to normal tissues and is notably high in ovarian tumors and B cell lymphomas. Motivated by the hypothesis that IL4I1 is an immuno-metabolic enzyme that suppresses anti-tumor immunity, we discovered CB-668, the first known small-molecule inhibitor of IL4I1.MethodsIL4I1 enzymatic activity was measured using an HRP-coupled enzyme assay. RNA in-situ hybridization was carried out on the RNAScope platform. Syngeneic mouse tumor models were used to evaluate the anti-tumor activity of CB-668. The level of phenyl-pyruvate in tumor homogenates was measured by LC/MS.ResultsOur clinical candidate, CB-668 is a potent and selective non-competitive inhibitor of IL4I1 (IC50 = 15 nM). CB-668 has favorable in vitro ADME properties and showed low clearance and high oral bioavailability in rodents. Twice-daily oral administration of CB-668 was well-tolerated in mice and resulted in single-agent anti-tumor activity in the syngeneic mouse tumor models B16-F10, A20, and EG7. Oral CB-668 administration reduced the levels of phenyl-pyruvate in the tumor, consistent with inhibition of IL4I1 enzymatic activity. Anti-tumor activity of CB-668 was immune cell-mediated since efficacy was abrogated in CD8-depleted mice, and CB-668 treatment caused increased expression of pro-inflammatory immune genes in the tumor. Moreover, CB-668 had no direct anti-proliferative activity on tumor cells grown in vitro (IC50 > 50 µM). CB-668 also favorably combined with anti-PD-L1 therapy to reduce tumor growth in the B16-F10 tumor model.ConclusionsThese data support an immune-mediated anti-tumor effect of IL4I1 inhibition by CB-668, and suggest inhibition of IL4I1 represents a novel strategy for cancer immuno-therapy.ReferencesMolinier-Frenkel V, Prévost-Blondel A, and Castellano F. The IL4I1 Enzyme: A New Player in the Immunosuppressive Tumor Microenvironment. Cells 2019;8:1–9.

Sign in / Sign up

Export Citation Format

Share Document