Dataset Information

Pattern-recognition receptors and gastric cancer.

ABSTRACT: Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy.

SUBMITTER: Castano-Rodriguez N

PROVIDER: S-EPMC4105827 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Pattern-recognition receptors and gastric cancer.

Castaño-Rodríguez Natalia N Kaakoush Nadeem O NO Mitchell Hazel M HM

Frontiers in immunology 20140722

Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recogni ...[more]

PMID: 25101079

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Project description:Endometriosis is closely associated with ectopic focal inflammation and immunosuppressive microenvironment. Multiple types of pattern recognition receptors (PRRs) are present in the innate immune system, which are able to detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in both intracellular and external environments. However, the exact role of PRRs in endometriosis and the underlying molecular mechanism are unclear. PRRs are necessary for the innate immune system to identify and destroy invasive foreign infectious agents. Mammals mainly have two types of microbial recognition systems. The first one consists of the membrane-bound receptors, such as toll-like receptors (TLRs), which recognize extracellular microorganisms and activate intracellular signals to stimulate immune responses. The second one consists of the intracellular PRRs, including nod-like receptors (NLRs) and antiviral proteins retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) with helix enzyme domain. In this review, we mainly focus on the key role of PRRs in the pathological processes associated with endometriosis. PRRs recognize PAMPs and can distinguish pathogenic microorganisms from self, triggering receptor ligand reaction followed by the stimulation of host immune response. Activated immune response promotes the transmission of microbial infection signals to the cells. As endometriosis is characterized by dysregulated inflammation and immune response, PRRs may potentially be involved in the activation of endometriosis-associated inflammation and immune disorders. Toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), nod-like receptor family caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5), nod-like receptor family pyrin domain containing 3 (NLRP3), and c-type lectin receptors (CLRs) play essential roles in endometriosis development by regulating immune and inflammatory responses. Absent in melanoma 2 (AIM2)-like receptors (ALRs) and retinoic acid-inducible gene I-like receptors (RLRs) may be involved in the activation of endometriosis-associated immune and inflammation disorders. PRRs, especially TLRs, may serve as potential therapeutic targets for alleviating pain in endometriosis patients. PRRs and their ligands interact with the innate immune system to enhance inflammation in the stromal cells during endometriosis. Thus, targeting PRRs and their new synthetic ligands may provide new therapeutic options for treating endometriosis.

Project description:In 2011, J. Hoffman, and B. Beutler won the Nobel Prize of medicine for the fact that they discovered the pattern recognition receptors (PRRs) and meanwhile described their effect on cell activation from the innate and adaptive immune systems. There are more and more evidences that have proved the obvious effect of PRRs on tumorigenesis progression. Nevertheless, the overall impact of PRR genes on prognosis, tumor microenvironmental characteristics and treatment response in patients with colon adenocarcinoma (COAD) remains unclear. In this research, we systematically assessed 20 PRR genes and comprehensively identified the prognostic value and enrichment degree of PRRs. The unsupervised clustering approach was employed for dividing COAD into 4 PRR subtypes, namely cluster A, cluster B, cluster C and cluster D, which were significantly different in terms of the clinical features, the immune infiltrations, and the functions. Among them, cluster B has better immune activities and functions. Cox and LASSO regression analysis was further applied to identify a prognostic five-PRR-based risk signature. Such signature can well predict patients' overall survival (OS), together with a good robustness. Confounding parameters were controlled, with results indicating the ability of risk score to independently predict COAD patients' OS. Besides, a nomogram with a strong reliability was created for enhancing the viability exhibited by the risk score in clinical practice. Also, patients who were classified based on the risk score owned distinguishable immune status and tumor mutation status, response to immunotherapy, as well as sensitivity to chemotherapy. A low risk score, featuring increased tumor stemness index (TSI), human leukocyte antigen (HLA), immune checkpoints, and immune activation, demonstrated a superior immunotherapeutic response. According to the study results, the prognostic PRR-based risk signature could serve as a robust biomarker for predicting the clinical outcomes as well as evaluating therapeutic response for COAD patients.

Dataset Information

Pattern-recognition receptors and gastric cancer.

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Pattern-recognition receptors and gastric cancer.

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