Opportunities and tradeoffs in single-cell transcriptomic technologies DOI Creative Commons
Matilde Immacolata Conte,

Azahara Fuentes‐Trillo,

Cecilia Domínguez Conde

et al.

Trends in Genetics, Journal Year: 2023, Volume and Issue: 40(1), P. 83 - 93

Published: Nov. 10, 2023

Recent technological and algorithmic advances enable single-cell transcriptomic analysis with remarkable depth breadth. Nonetheless, a persistent challenge is the compromise between ability to profile high numbers of cells achievement full-length transcript coverage. Currently, field progressing developing new creative solutions that improve cellular throughput, gene detection sensitivity capture. Furthermore, long-read sequencing approaches for transcripts are breaking frontiers have previously blocked full transcriptome characterization. We here present comprehensive overview available options profiling, highlighting key advantages disadvantages each approach.

Language: Английский

Neoantigens: promising targets for cancer therapy DOI Creative Commons
Na Xie, Guobo Shen, Wei Gao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 6, 2023

Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by cells as a result various tumor-specific alterations, such genomic mutation, dysregulated RNA splicing, disordered post-translational modification, integrated viral open reading frames. recognized non-self trigger an immune response that is not subject to central peripheral tolerance. The quick identification prediction neoantigens been made possible advanced next-generation sequencing bioinformatic technologies. Compared tumor-associated antigens, highly immunogenic provide emerging targets personalized serve prospective predictors survival prognosis checkpoint blockade responses. therapies will be aided understanding mechanism underlying neoantigen-induced anti-tumor streamlining process neoantigen-based immunotherapies. This review provides overview on characterization outlines clinical applications immunotherapeutic strategies based neoantigens. We also explore their current status, inherent challenges, translation potential.

Language: Английский

Citations

483
Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions DOI Creative Commons
Daniel Butler, Christopher Mozsary, Cem Meydan

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 12, 2021

Abstract In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed fast (30-minute) colorimetric test (LAMP) for infection from naso/oropharyngeal swabs large-scale shotgun metatranscriptomics platform (total-RNA-seq) host, viral, microbial profiling. We applied methods specimens gathered 669 patients during first two months outbreak, yielding broad molecular portrait emerging disease. find significant enrichment NYC-distinctive clade virus (20C), as well host responses interferon, ACE, hematological, olfaction pathways. addition, use 50,821 patient records that renin–angiotensin–aldosterone system inhibitors have protective effect severe outcomes, unlike similar drugs. Finally, spatial transcriptomic data autopsy tissues reveal distinct ACE2 expression loci, with macrophage neutrophil infiltration lungs. These findings can inform public health may help develop drive diagnostic, prevention, treatment strategies.

Language: Английский

Citations

175
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

148
Challenges in neoantigen-directed therapeutics DOI Creative Commons
Lien Lybaert, Steve Lefever, Bruno Fant

et al.

Cancer Cell, Journal Year: 2022, Volume and Issue: 41(1), P. 15 - 40

Published: Nov. 10, 2022

Language: Английский

Citations

79
LAG-3 and PD-1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity DOI
Lawrence P. Andrews, Samuel C. Butler, Jian Cui

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(16), P. 4355 - 4372.e22

Published: Aug. 1, 2024

Language: Английский

Citations

69
The immunopeptidome landscape associated with T cell infiltration, inflammation and immune editing in lung cancer DOI Creative Commons

Anne I. Kraemer,

Chloé Chong,

Florian Huber

et al.

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(5), P. 608 - 628

Published: May 1, 2023

Abstract One key barrier to improving efficacy of personalized cancer immunotherapies that are dependent on the tumor antigenic landscape remains patient stratification. Although patients with CD3 + CD8 T cell-inflamed tumors typically show better response immune checkpoint inhibitors, it is still unknown whether immunopeptidome repertoire presented in highly inflamed and noninflamed substantially different. We surveyed 61 regions adjacent nonmalignant lung tissues from 8 performed deep antigen discovery combining immunopeptidomics, genomics, bulk spatial transcriptomics, explored heterogeneous expression presentation (neo)antigens. In present study, we associated diverse cell populations found a relatively higher frequency predicted neoantigens located within HLA-I hotspots cell-excluded tumors. such recognition, supporting their involvement editing. This could have implications for choice combination therapies tailored patient’s mutanome microenvironment.

Language: Английский

Citations

50
Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy DOI
Guangyuan Li, Shweta Mahajan, Siyuan Ma

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(730)

Published: Jan. 17, 2024

Immunotherapy has emerged as a crucial strategy to combat cancer by “reprogramming” patient’s own immune system. Although immunotherapy is typically reserved for patients with high mutational burden, neoantigens produced from posttranscriptional regulation may provide an untapped reservoir of common immunogenic targets new targeted therapies. To comprehensively define tumor-specific and likely patient RNA-Seq, we developed Splicing Neo Antigen Finder (SNAF), easy-to-use open-source computational workflow predict splicing-derived MHC-bound peptides (T cell antigen) unannotated transmembrane proteins altered extracellular epitopes (B antigen). This uses highly accurate deep learning immunogenicity prediction (DeepImmuno) in conjunction algorithms rank the tumor specificity (BayesTS) regulators mis-splicing (RNA-SPRINT). T antigens SNAF were frequently evidenced HLA-presented mass spectrometry (MS) response melanoma. neoantigen burden was attributed coordinated splicing factor dysregulation. Shared found up 90% melanoma, correlated overall survival multiple cohorts, induced reactivity, characterized distinct cells origin amino acid preferences. In addition neoantigens, our B focused pipeline (SNAF-B) identified class neoepitopes, which termed ExNeoEpitopes. ExNeoEpitope full-length mRNA predictions specific validated using long-read isoform sequencing vitro localization assays. Therefore, systematic identification revealed potential shared therapy heterogeneous cancers.

Language: Английский

Citations

32
Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis DOI
Joona Sarkkinen, Dawit Yohannes,

Nea Kreivi

et al.

Science Immunology, Journal Year: 2025, Volume and Issue: 10(104)

Published: Feb. 21, 2025

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection a prerequisite for developing disease. However, pathogenic mechanisms that lead to MS remain be determined. Here, we characterized immune landscape deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing cellular indexing transcriptomes epitopes by sequencing, observed increased memory B cells reduced germinal center decreased clonality pwMS. Double-negative were pwMS transcriptionally resembled lytic EBV infection. Moreover, EBV-targeting CD8 T detected subset We also DNA dcLNs elevated viral loads patient saliva. These findings suggest EBV-driven cell dysregulation critical mechanism pathogenesis.

Language: Английский

Citations

2
Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group DOI Creative Commons
Leticia De Mattos‐Arruda, Miguél Vázquez, Francesca Finotello

et al.

Annals of Oncology, Journal Year: 2020, Volume and Issue: 31(8), P. 978 - 990

Published: June 28, 2020

Language: Английский

Citations

120
Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01 DOI Creative Commons
January Weiner, Phillip Suwalski, Manuel Holtgrewe

et al.

EClinicalMedicine, Journal Year: 2021, Volume and Issue: 40, P. 101099 - 101099

Published: Sept. 2, 2021

BackgroundSince the beginning of coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading severe clinical course in patients infected with acute respiratory syndrome 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have suggested as potential genetic host factors that affect individual immune response SARS-CoV-2. We sought evaluate this hypothesis by conducting a multicenter study using HLA sequencing.MethodsWe analyzed association between COVID-19 severity and HLAs 435 individuals from Germany (n = 135), Spain 133), Switzerland 20) United States 147), who had enrolled March 2020 August 2020. This included older than 18 years, diagnosed representing full spectrum disease. Finally, we tested our results meta-analysing data prior genome-wide studies (GWAS).FindingsWe describe HLA-C*04:01 COVID-19. Carriers twice risk intubation when SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1–2.1], odds 3.5 1.9–6.6], adjusted p-value 0.0074). These findings are based on four countries corroborated independent GWAS. Our biologically plausible, fewer predicted bindings sites for relevant peptides compared other alleles.InterpretationHLA-C*04:01 carrier state is associated suggest class I role defense against SARS-CoV-2.FundingFunded Roche Sequencing Solutions, Inc.

Language: Английский

Citations

90