A blueprint for tumor-infiltrating B cells across human cancers DOI
Jiaqiang Ma, Yingcheng Wu, Lifeng Ma

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6695)

Published: May 2, 2024

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions tumor-infiltrating cells, we generated a cell blueprint encompassing single-cell transcriptome, cell-receptor repertoire, chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). cells harbored extraordinary heterogeneity comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor extrafollicular pathway were linked with worse clinical outcomes resistance to immunotherapy. The dysfunctional program was associated glutamine-derived metabolites through epigenetic-metabolic cross-talk, promoted T cell-driven immunosuppressive program. These suggest an intratumor balance between germinal-center responses that possibly harnessed for cell-targeting

Language: Английский

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

Citations

180

Best practices for bioinformatic characterization of neoantigens for clinical utility DOI Creative Commons
Megan M. Richters, Huiming Xia, Katie M. Campbell

et al.

Genome Medicine, Journal Year: 2019, Volume and Issue: 11(1)

Published: Aug. 28, 2019

Neoantigens are newly formed peptides created from somatic mutations that capable of inducing tumor-specific T cell recognition. Recently, researchers and clinicians have leveraged next generation sequencing technologies to identify neoantigens create personalized immunotherapies for cancer treatment. To a vaccine, must be computationally predicted matched tumor-normal data, then ranked according their capability in stimulating response. This candidate neoantigen prediction process involves multiple steps, including mutation identification, HLA typing, peptide processing, peptide-MHC binding prediction. The general workflow has been utilized many preclinical clinical trials, but there is no current consensus approach few established best practices. In this article, we review recent discoveries, summarize the available computational tools, provide analysis considerations each step, prediction, prioritization, delivery, validation methods. addition reviewing state analysis, practical guidance, specific recommendations, extensive discussion critical concepts points confusion practice characterization use. Finally, outline necessary areas development, need improve class II typing accuracy, expand software support diverse sources, incorporate response data algorithms. ultimate goal workflows vaccines patient outcomes types.

Language: Английский

Citations

176

Deconvoluting tumor-infiltrating immune cells from RNA-seq data using quanTIseq DOI
Christina Plattner, Francesca Finotello, Dietmar Rieder

et al.

Methods in enzymology on CD-ROM/Methods in enzymology, Journal Year: 2019, Volume and Issue: unknown, P. 261 - 285

Published: June 22, 2019

Language: Английский

Citations

172

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids DOI Creative Commons
Nicolas Alcala, Noémie Leblay, Alice‐Agnes Gabriel

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 20, 2019

Abstract The worldwide incidence of pulmonary carcinoids is increasing, but little known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare contrast the genomic profiles 116 (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), 66 small-cell lung cancers. Here report that integrative analyses on 257 neoplasms stratify atypical into two prognostic groups with a 10-year overall survival 88% 27%, respectively. We identify therapeutically relevant carcinoids, suggesting DLL3 immune system as candidate therapeutic targets; confirm value OTP expression levels for prognosis diagnosis these diseases, unveil group supra-carcinoids. This comprises samples carcinoid-like morphology yet clinical features deadly LCNEC, further supporting previously proposed link between low- high-grade neoplasms.

Language: Английский

Citations

169

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade DOI Creative Commons
Carlo Genova, Chiara Dellepiane, Paolo Carrega

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 7, 2022

In the last decade, treatment of non-small cell lung cancer (NSCLC) has been revolutionized by introduction immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). spite these improvements, some patients do not achieve any benefit from ICI, inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response immunotherapy due prominent role in multiple interactions between neoplastic cells system. Studies investigating perspective TME pointed out a complex scenario where tumor angiogenesis, soluble factors, suppressive/regulatory elements composing itself participate growth. this review, we point current state knowledge involving relationship components NSCLC as well their with providing an update on novel predictors currently employed ICI new therapeutic targets investigational agents. first place, increasing evidence suggests that represent promising biomarker sensitivity based presence immune-modulating cells, such Treg, myeloid derived suppressor associated macrophages, which are known induce immunosuppressive environment, poorly responsive ICI. Consequently, clinical studies have designed towards pro-immunogenic subsequently improve activity Currently, mostly approach relies association “classic” targeting PD-1/PD-L1 agents molecules, LAG-3 TIM-3. To date, trials already shown results, while multitude prospective ongoing, results significantly future immunotherapy.

Language: Английский

Citations

161

Next-generation computational tools for interrogating cancer immunity DOI
Francesca Finotello, Dietmar Rieder, Hubert Hackl

et al.

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(12), P. 724 - 746

Published: Sept. 12, 2019

Language: Английский

Citations

147

In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target DOI Creative Commons
Xiaoqing Wang, Collin Tokheim, Shengqing Gu

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(21), P. 5357 - 5374.e22

Published: Sept. 27, 2021

Language: Английский

Citations

134

Molecular Characterization ofKRASWild-type Tumors in Patients with Pancreatic Adenocarcinoma DOI Open Access
Philip A. Philip, Ibrahim Azar, Joanne Xiu

et al.

Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 28(12), P. 2704 - 2714

Published: March 18, 2022

KRAS mutation (MT) is a major oncogenic driver in pancreatic ductal adenocarcinoma (PDAC). A small subset of PDACs harbor wild-type (WT). We aim to characterize the molecular profiles WT PDAC uncover new pathogenic drivers and offer targeted treatments.

Language: Английский

Citations

122

Characterization of PANoptosis patterns predicts survival and immunotherapy response in gastric cancer DOI

Hongda Pan,

Jingxin Pan,

Pei Li

et al.

Clinical Immunology, Journal Year: 2022, Volume and Issue: 238, P. 109019 - 109019

Published: April 22, 2022

Language: Английский

Citations

101

Neutrophil profiling illuminates anti-tumor antigen-presenting potency DOI Creative Commons
Yingcheng Wu, Jiaqiang Ma, Xupeng Yang

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(6), P. 1422 - 1439.e24

Published: March 1, 2024

Language: Английский

Citations

95