Hiplot: a comprehensive and easy-to-use web service for boosting publication-ready biomedical data visualization DOI
Jianfeng Li, Ben‐Ben Miao, Shixiang Wang

et al.

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 23(4)

Published: July 5, 2022

Abstract Complex biomedical data generated during clinical, omics and mechanism-based experiments have increasingly been exploited through cloud- visualization-based mining techniques. However, the scientific community still lacks an easy-to-use web service for comprehensive visualization of data, particularly high-quality publication-ready graphics that allow easy scaling updatability according to user demands. Therefore, we propose a community-driven modern service, Hiplot (https://hiplot.org), with concise top-quality applications life sciences fields. This permits users conveniently interactively complete few specialized tasks previously could only be conducted by senior bioinformatics or biostatistics researchers. It covers most daily demands researchers its equipped 240+ functions, involving basic statistics, multi-omics, regression, clustering, dimensional reduction, meta-analysis, survival analysis, risk modelling, etc. Moreover, improve efficiency in use development plugins, introduced some core advantages on client-/server-side website, such as spreadsheet-based importing, cross-platform command-line controller (Hctl), multi-user plumber workers, JavaScript Object Notation-based plugin system, data/parameters, results errors reproduction real-time updates mode. Meanwhile, using demo/real sets benchmark tests, explored statistical parameters, cancer genomic landscapes, disease factors performance website based selected native plugins. The statistics visits numbers further reflect potential impact this relevant Thus, devoted would benefit from emerging free service.

Language: Английский

Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells DOI Open Access
Takahiro Kamiya,

See Voon Seow,

Desmond Wong

et al.

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(5), P. 2094 - 2106

Published: March 12, 2019

A key mechanism of tumor resistance to immune cells is mediated by expression peptide-loaded HLA class I molecule (HLA-E) in cells, which suppresses NK cell activity via ligation the inhibitory receptor CD94/NK group 2 member (NKG2A). Gene data from approximately 10,000 samples showed widespread HLAE expression, with levels correlating those KLRC1 (NKG2A) and KLRD1 (CD94). To bypass HLA-E inhibition, we developed a way generate highly functional lacking NKG2A. Constructs containing single-chain variable fragment derived an anti-NKG2A antibody were linked endoplasmic reticulum–retention domains. After retroviral transduction human peripheral blood these NKG2A protein blockers (PEBLs) abrogated expression. The resulting NKG2Anull had higher cytotoxicity against HLA-E–expressing cells. Transduction PEBL produced more potent than interference prevented de novo without affecting proliferation. In immunodeficient mice, substantially powerful NKG2A+ tumors. Thus, downregulation evades cancer checkpoint increases antitumor infusions. Because this strategy easily adaptable current protocols for clinical-grade processing, its clinical testing feasible warranted.

Language: Английский

Citations

284
METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer DOI Creative Commons
Weijun Wan, Xiang Ao, Quan Chen

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 23, 2022

Abstract Background Continual expression of PD-L1 in tumor cells is critical for immune escape and host T cell exhaustion, however, knowledge on its clinical benefits through inhibition limited breast cancer. N 6 -methyladenosine (m A) plays a crucial role multiple biological activities. Our study aimed to investigate the regulatory m A modification surveillance Methods MeRIP-seq epitranscriptomic microarray identified that downstream target METTL3. MeRIP-qPCR, absolute quantification assay, RIP-qPCR were used examine molecular mechanism underlying METTL3/m A/IGF2BP3 signaling axis expression. B-NDG BALB/c mice construct xenograft models verify phenotypes upon METTL3 IGF2BP3 silencing. In addition, cancer tissue was analyze correlation between or Results We METTL3-mediated cells. knockdown significantly abolished reduced stabilization mRNA. Additionally, mRNA activation A-IGF2BP3-dependent. Moreover, enhanced anti-tumor immunity PD-L1-mediated activation, infiltration both vitro vivo. also positively correlated with tissues. Conclusion suggested could post-transcriptionally upregulate an A-IGF2BP3-dependent manner further promote mRNA, which may have important implications new efficient therapeutic strategies immunotherapy.

Language: Английский

Citations

268
A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma DOI Open Access
Zilong Bian, Rong Fan, Lingmin Xie

et al.

Genes, Journal Year: 2022, Volume and Issue: 13(5), P. 851 - 851

Published: May 10, 2022

Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of carcinoma, which characterized by metabolic reprogramming. Cuproptosis, a novel form death, highly linked to mitochondrial metabolism and mediated protein lipoylation. However, clinical impacts cuproptosis-related genes (CRGs) in ccRCC largely remain unclear. In current study, we systematically evaluated genetic alterations ccRCC. Our results revealed that CDKN2A, DLAT, DLD, FDX1, GLS, PDHA1 PDHB exhibited differential expression between normal tissues (|log2(fold change)| > 2/3 p < 0.05). Utilizing an iterative sure independence screening (SIS) method, separately constructed prognostic signature CRGs for predicting overall survival (OS) progression-free (PFS) patients. The score yielded area under curve (AUC) 0.658 0.682 prediction 5-year OS PFS, respectively. Kaplan−Meier analysis OS, higher risk gene was significantly correlated with worse (HR = 2.72 (2.01−3.68), log-rank 1.76 × 10−7). Patients had shorter PFS 2.83 (2.08−3.85), 3.66 Two independent validation datasets (GSE40435 (N 101), GSE53757 72)) were collected meta-analysis, suggesting CDKN2A (log2(fold change) 1.46, 95%CI: 1.75−2.35) showed while DLAT −0.54, −0.93−−0.15) FDX1 −1.01, −1.61−−0.42) lowly expressed. also associated immune infiltration levels programmed death 1 (PD-1) (CDKN2A: r 0.24, 2.14 10−8; FDX1: −0.17, 1.37 10−4). conclusion, could serve as potential predictor patients may offer insights into cancer treatment.

Language: Английский

Citations

263
Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response DOI
Feifei Hu, Chunjie Liu, Lanlan Liu

et al.

Briefings in Bioinformatics, Journal Year: 2020, Volume and Issue: 22(3)

Published: July 15, 2020

Abstract Immune checkpoint genes (ICGs) play critical roles in circumventing self-reactivity and represent a novel target to develop treatments for cancers. However, comprehensive analysis the expression profile of ICGs at pan-cancer level their correlation with patient response immune blockade (ICB) based therapy is still lacking. In this study, we defined three patterns using survey RNA-seq data tumor cells from functional annotation mammalian genome (FANTOM5) project. The between patients survival ICB was investigated. were robust across cancers, upregulation positively correlated high lymphocyte infiltration good prognosis. Furthermore, built model (ICGe) predict five features ICG expression. A validation scenario six independent datasets containing 261 CTLA-4 PD-1 immunotherapies demonstrated that ICGe achieved area under curves 0.64–0.82 showed performance outperformed other mRNA-based predictors. conclusion, work revealed underlying correlations ICB, which helps understand mechanisms signal pathways anticancer treatments.

Language: Английский

Citations

257
Stress–glucocorticoid–TSC22D3 axis compromises therapy-induced antitumor immunity DOI
Heng Yang, Lin Xia, Jian Chen

et al.

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(9), P. 1428 - 1441

Published: Sept. 1, 2019

Language: Английский

Citations

256
Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance DOI Creative Commons
Yi Liu, Guanghao Liang, Hongjiao Xu

et al.

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(6), P. 1221 - 1233.e11

Published: April 27, 2021

Language: Английский

Citations

241
Blocking Triggering Receptor Expressed on Myeloid Cells‐1‐Positive Tumor‐Associated Macrophages Induced by Hypoxia Reverses Immunosuppression and Anti‐Programmed Cell Death Ligand 1 Resistance in Liver Cancer DOI Creative Commons
Qinchuan Wu,

Wuhua Zhou,

Shengyong Yin

et al.

Hepatology, Journal Year: 2019, Volume and Issue: 70(1), P. 198 - 214

Published: Feb. 27, 2019

Tumor‐associated macrophages (TAMs) are recognized as antitumor suppressors, but how TAMs behave in the hypoxic environment of hepatocellular carcinoma (HCC) remains unclear. Here, we demonstrated that hypoxia inducible factor 1α induced increased expression triggering receptor expressed on myeloid cells‐1 (TREM‐1) TAMs, resulting immunosuppression. Specifically, TREM‐1‐positive (TREM‐1 + ) abundant at advanced stages HCC progression indirectly impaired cytotoxic functions CD8 T cells and T‐cells apoptosis. Biological functional assays showed TREM‐1 had higher programmed cell death ligand 1 (PD‐L1) under environment. However, could abrogate spontaneous PD‐L1‐blockade‐mediated effects vivo , suggesting TAM‐induced immunosuppression was dependent a pathway separate from PD‐L1/programmed axis. Moreover, TAM‐associated regulatory (Tregs) were crucial for resistance to anti‐PD‐L1 therapy. Mechanistically, elevated chemokine (C‐C motif) 20 through extracellular signal‐regulated kinase/NF‐κβ response tumor metabolites leading CCR6 Foxp3 Treg accumulation. Blocking significantly inhibit progression, reduce recruitment, improve therapeutic efficacy PD‐L1 blockade. Thus, these data recruitment TAM‐mediated Conclusion : This study highlighted initiated onset attracting Tregs, endowed with therapy resistance.

Language: Английский

Citations

222
Tumor microenvironment promotes breast cancer chemoresistance DOI
Umar Mehraj,

Abid Hamid Dar,

Nissar Ahmad Wani

et al.

Cancer Chemotherapy and Pharmacology, Journal Year: 2021, Volume and Issue: 87(2), P. 147 - 158

Published: Jan. 9, 2021

Language: Английский

Citations

212
CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance DOI Creative Commons
Cheng Wang, Yang Li, Lingfei Jia

et al.

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(9), P. 1597 - 1613.e7

Published: May 3, 2021

Language: Английский

Citations

210
Unraveling tumor–immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy DOI
Alejandro Jiménez-Sánchez, Paulina Cybulska,

Katherine LaVigne Mager

et al.

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(6), P. 582 - 593

Published: June 1, 2020

Language: Английский

Citations

186