Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer

Lin, Chao; He, Hongyong; Líu, Hao; Li, Ruochen; Chen, Yifan; Qi, Yangyang; Jiang, Qi; Chen, Lingli; Zhang, Peipei; Zhang, Heng; Li, He; Zhang, Weijuan; Sun, Yihong; Xu, Jiejie

doi:10.1136/gutjnl-2018-316324

Cited by 250 publications

(208 citation statements)

References 32 publications

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“…Interruption of the related signaling pathways may thus provide promising therapeutic avenues for tumors. Studies have found that CXCL8 is predominantly secreted by macrophages and contributes to the immunosuppressive microenvironment by inducing PD-L1 + macrophages in GC [52]. CXCL8 inhibitors may drive antitumor response, providing potential therapeutic effects for patients with gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Hub Genes Associated With Gastric Cancer Using Integrated Bioinformatics Analysis

Zhang

Qiao

et al. 2020

Preprint

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Background: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy.Methods: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytoHubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. Results: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients.Discussion: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Hub Genes Associated With Gastric Cancer Using Integrated Bioinformatics Analysis

Zhang

Qiao

et al. 2020

Preprint

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“…IL-6 secreted by intraperitoneal TAMs promotes peritoneal dissemination of GC [163]. CXCL-8 present in the GC stroma is secreted mostly by macrophages, leading to an increased expression of PD-L1 on their surface [164]. This reduces CD8+ T-cells infiltration and impairs the anti-tumor immune response.…”

Section: Tumor-associated Macrophages In Gastric Cancermentioning

confidence: 99%

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

Baj

Brzozowska

Forma

et al. 2020

IJMS

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Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer.EMT refers to the process by which the mesenchymal phenotype is acquired by epithelial cells (ECs) mainly via the reduction of their intracellular adhesions and proliferative capacity (Figure 1.) [47].

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“…High CXCL8 secretion was associated with decreased CD8 + T cell infiltration, proliferation and function by inducing the expression of PD‐L1 on macrophages. The authors found that the small molecule CXR2 inhibitor (reparixin) drives the decreased PD‐L1 + macrophages and promotes antitumour immunity, providing potential therapeutic effects for GC patients 19 …”

Section: Immune Microenvironmentmentioning

confidence: 99%

Review: Gastric cancer: Basic aspects

2020

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Gastric cancer is still one of the most prevalent and deadliest cancers in the world. Although our knowledge about the disease has progressed extraordinarily, this has not been accompanied by our capacity to effectively treat the disease. In the last years, immunotherapy made its way into the cancer field and was responsible for major changes in the treatment success rates for several cancer types. Although gastric cancer was not among the first successful targets of this type of therapy, the relationship between this type of cancer, immunosurveillance and immunotherapy is now being actively researched. In this article, we review the literature of the past year regarding the relationship between gastric cancer, its immune microenvironment and response to immunotherapy. Published data indicate that the immune microenvironment influences the clinical behaviour of gastric cancer, and is correlated with its histologic and molecular subtypes with an emphasis on the microsatellite‐ and EBV‐positive tumour subgroups. Although the literature regarding response to immunotherapy is scarce, there is good evidence that patient stratification for immunotherapy is going to become a reality in gastric cancer.

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Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer

Cited by 250 publications

References 32 publications

Identification of Novel Hub Genes Associated With Gastric Cancer Using Integrated Bioinformatics Analysis

Identification of Novel Hub Genes Associated With Gastric Cancer Using Integrated Bioinformatics Analysis

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

Review: Gastric cancer: Basic aspects

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