Comprehensive molecular profiling of the B7 family in gastrointestinal cancer

Zhao, Qijie; Hu, Fuyan; Xiao, Zhangang; Li, Mingxing; Wu, Xu; Zhao, Yueshui; Wu, Yifan; Yin, Jianhua; Lin, Ling; Zhang, Hanyu; Zhang, Lingling; Cho, Chi Hin; Shen, Jing

doi:10.1111/cpr.12468

Cited by 10 publications

(9 citation statements)

References 63 publications

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“…It plays an important role in Natural Killer (NK) cells mediated immune responses and is thought to be involved in tumor progression of various types of human cancers. [44][45][46] Our results indicate that patients with low leptin levels and T2D should be paid more attention to their immune system.…”

Section: Discussionmentioning

confidence: 71%

Shared genetic architecture and casual relationship between leptin levels and type 2 diabetes: large-scale cross-trait meta-analysis and Mendelian randomization analysis

Wang

Jia

Huang

2020

BMJ Open Diab Res Care

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ObjectiveWe aimed to estimate genetic correlation, identify shared loci and test causality between leptin levels and type 2 diabetes (T2D).Research design and methodsOur study consists of three parts. First, we calculated the genetic correlation of leptin levels and T2D or glycemic traits by using linkage disequilibrium score regression analysis. Second, we conducted a large-scale genome-wide cross-trait meta-analysis using cross-phenotype association to identify shared loci between trait pairs that showed significant genetic correlations in the first part. In the end, we carried out a bidirectional MR analysis to find out whether there is a causal relationship between leptin levels and T2D or glycemic traits.ResultsWe found positive genetic correlations between leptin levels and T2D (Rg=0.3165, p=0.0227), fasting insulin (FI) (Rg=0.517, p=0.0076), homeostasis model assessment-insulin resistance (HOMA-IR) (Rg=0.4785, p=0.0196), as well as surrogate estimates of β-cell function (HOMA-β) (Rg=0.4456, p=0.0214). We identified 12 shared loci between leptin levels and T2D, 1 locus between leptin levels and FI, 1 locus between leptin levels and HOMA-IR, and 1 locus between leptin levels and HOMA-β. We newly identified eight loci that did not achieve genome-wide significance in trait-specific genome-wide association studies. These shared genes were enriched in pancreas, thyroid gland, skeletal muscle, placenta, liver and cerebral cortex. In addition, we found that 1-SD increase in HOMA-IR was causally associated with a 0.329 ng/mL increase in leptin levels (β=0.329, p=0.001).ConclusionsOur results have shown the shared genetic architecture between leptin levels and T2D and found causality of HOMA-IR on leptin levels, shedding light on the molecular mechanisms underlying the association between leptin levels and T2D.

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Section: Discussionmentioning

confidence: 71%

Shared genetic architecture and casual relationship between leptin levels and type 2 diabetes: large-scale cross-trait meta-analysis and Mendelian randomization analysis

Wang

Jia

Huang

2020

BMJ Open Diab Res Care

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“…Increased or aberrant PD-L1 expression in both epithelial compartments and immune cells has been demonstrated in several diseases, including several types of (gastrointestinal) cancers [34][35][36][37][38][39][40][41] and gastric adenocarcinomas. 42 However, the timing within the carcinogenesis cascade at which this expression pattern starts to deviate is unclear.…”

Section: Discussionmentioning

confidence: 99%

Constitutive programmed death ligand 1 expression protects gastric G‐cells from Helicobacter pylori–induced inflammation

Mommersteeg

Bosch

et al. 2022

Helicobacter

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Introduction Gastric intestinal metaplasia (GIM) is a premalignant lesion, highly associated with Helicobacter pylori infection. Previous studies have shown that H. pylori is able to induce the expression of programmed death ligand 1 (PD‐L1), an inhibitory immune modulator, in gastric cells. Our aim was to investigate whether tissues from GIM patients may exploit PD‐L1 expression upon H. pylori infection to evade immunosurveillance. Methods Immunohistochemistry was performed for PD‐L1 and enteroendocrine markers somatostatin and gastrin on samples derived from a cohort of patients with known GIM, both before and after H. pylori eradication. To determine the identity of any observed PD‐L1‐positive cells, we performed multiplex immunofluorescent staining and analysis of single‐cell sequencing data. Results GIM tissue was rarely positive for PD‐L1. In normal glands from GIM patients, PD‐L1 was mainly expressed by gastrin‐positive G‐cells. While the D‐cell and G‐cell compartments were both diminished 2‐fold (p = .015 and p = .01, respectively) during H. pylori infection in the normal antral tissue of GIM patients, they were restored 1 year after eradication. The total number of PD‐L1‐positive cells was not affected by H. pylori, but the percentage of PD‐L1‐positive G‐cells was 30% higher in infected subjects (p = .011), suggesting that these cells are preferentially rescued from destruction. Conclusions Antral G‐cells frequently express PD‐L1 during homeostasis. G‐cells seem to be protected from H. pylori‐induced immune destruction by PD‐L1 expression. GIM itself does not express PD‐L1 and is unlikely to escape immunosurveillance via expression of PD‐L1.

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“…PD-L1 is expressed on leukocytes, non-hematopoietic cells, non-lymphoid tissues as well as in parenchymal cells through tumorigenic signals or inflammatory cytokines 55 . Expression of PD-L1 is differently identified in several tumor types and is incorporated with the increase and decrease of the amount of TILs and prognosis, respectively 56 , 57 , 58 . The expression of PD-L2 is considerable in DCs and monocytes and can be triggered depending on the microenvironment by a broad range of particular immune and non-immune cells 59 .…”

Section: Immune Checkpoint Pathwaysmentioning

confidence: 99%

Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Kiaie

Sanaei

Heshmati

et al. 2021

Acta Pharmaceutica Sinica B

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Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.

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Comprehensive molecular profiling of the B7 family in gastrointestinal cancer

Abstract: Overall, our study suggested that B7 member deregulation was strongly involved in GI cancer tumorigenesis.

Cited by 10 publications

References 63 publications

Shared genetic architecture and casual relationship between leptin levels and type 2 diabetes: large-scale cross-trait meta-analysis and Mendelian randomization analysis

Shared genetic architecture and casual relationship between leptin levels and type 2 diabetes: large-scale cross-trait meta-analysis and Mendelian randomization analysis

Constitutive programmed death ligand 1 expression protects gastric G‐cells from Helicobacter pylori–induced inflammation

Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

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