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

m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer DOI Creative Commons
Bo Zhang, Qiong Wu, Ben Li

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: March 12, 2020

The epigenetic regulation of immune response has been demonstrated in recent studies. Nonetheless, potential roles RNA N6-methyladenosine (m6A) modification tumor microenvironment (TME) cell infiltration remain unknown.We comprehensively evaluated the m6A patterns 1938 gastric cancer samples based on 21 regulators, and systematically correlated these with TME cell-infiltrating characteristics. m6Ascore was constructed to quantify individual tumors using principal component analysis algorithms.Three distinct were determined. characteristics under three highly consistent phenotypes including immune-excluded, immune-inflamed immune-desert phenotypes. We evaluation within could predict stages inflammation, subtypes, stromal activity, genetic variation, patient prognosis. Low m6Ascore, characterized by increased mutation burden activation immunity, indicated an inflamed phenotype, 69.4% 5-year survival. Activation stroma lack effective observed high subtype, indicating a non-inflamed immune-exclusion poorer also linked neoantigen load enhanced anti-PD-1/L1 immunotherapy. Two immunotherapy cohorts confirmed patients lower significant therapeutic advantages clinical benefits.This work revealed played nonnegligible role formation diversity complexity. Evaluating pattern will contribute enhancing our cognition characterization guiding more strategies.

Language: Английский

Citations

787
Neoantigen-directed immune escape in lung cancer evolution DOI Open Access
Rachel Rosenthal, Elizabeth Larose Cadieux,

Roberto Salgado

et al.

Nature, Journal Year: 2019, Volume and Issue: 567(7749), P. 479 - 485

Published: March 1, 2019

Language: Английский

Citations

779
Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features DOI
Daniela Sia, Yang Jiao,

Iris Martinez-Quetglas

et al.

Gastroenterology, Journal Year: 2017, Volume and Issue: 153(3), P. 812 - 826

Published: June 16, 2017

Language: Английский

Citations

760
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets DOI Creative Commons
Luca Cassetta, Stamatina Fragkogianni, Andrew H. Sims

et al.

Cancer Cell, Journal Year: 2019, Volume and Issue: 35(4), P. 588 - 602.e10

Published: March 28, 2019

The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution transcriptomes significantly altered by the presence endometrial breast cancer. Furthermore, TAMs from cancers transcriptionally distinct their respective tissue-resident macrophages. We identified a TAM signature is highly enriched aggressive subtypes associated with shorter disease-specific survival. also an auto-regulatory loop between cells driven tumor necrosis factor alpha involving SIGLEC1 CCL8, which self-reinforcing through production CSF1. Together these data provide direct evidence macrophage transcriptional landscapes perturbed cancer, reflecting patient outcomes.

Language: Английский

Citations

758
IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures DOI Creative Commons
Dongqiang Zeng,

Zilan Ye,

Rongfang Shen

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 2, 2021

Recent advances in next-generation sequencing (NGS) technologies have triggered the rapid accumulation of publicly available multi-omics datasets. The application integrated omics to explore robust signatures for clinical translation is increasingly emphasized, and this attributed success immune checkpoint blockades diverse malignancies. However, effective tools comprehensively interpreting data are still warranted provide increased granularity into intrinsic mechanism oncogenesis immunotherapeutic sensitivity. Therefore, we developed a computational tool Immuno-Oncology Biological Research (IOBR), providing comprehensive investigation estimation reported or user-built signatures, TME deconvolution, signature construction based on data. Notably, IOBR offers batch analyses these their correlations with phenotypes, long non-coding RNA (lncRNA) profiling, genomic characteristics, generated from single-cell (scRNA-seq) different cancer settings. Additionally, integrates multiple existing microenvironmental deconvolution methodologies convenient comparison selection. Collectively, user-friendly leveraging facilitate immuno-oncology exploration unveil tumor-immune interactions accelerating precision immunotherapy.

Language: Английский

Citations

733
Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors DOI Creative Commons
Denarda Dangaj, Marine Bruand, Alizée J. Grimm

et al.

Cancer Cell, Journal Year: 2019, Volume and Issue: 35(6), P. 885 - 900.e10

Published: June 1, 2019

Language: Английский

Citations

646
Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer DOI Creative Commons
James B. Wing, Atsushi Tanaka, Shimon Sakaguchi

et al.

Immunity, Journal Year: 2019, Volume and Issue: 50(2), P. 302 - 316

Published: Feb. 1, 2019

Language: Английский

Citations

586
Integrating oncolytic viruses in combination cancer immunotherapy DOI
Praveen K. Bommareddy, Megha Shettigar, Howard L. Kaufman

et al.

Nature reviews. Immunology, Journal Year: 2018, Volume and Issue: 18(8), P. 498 - 513

Published: May 9, 2018

Language: Английский

Citations

562
Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade DOI Open Access
Steve Lu,

Julie E. Stein,

David L. Rimm

et al.

JAMA Oncology, Journal Year: 2019, Volume and Issue: 5(8), P. 1195 - 1195

Published: July 18, 2019

Importance

PD-L1 (programmed cell death ligand 1) immunohistochemistry (IHC), tumor mutational burden (TMB), gene expression profiling (GEP), and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) assays have been used to assess pretreatment tissue predict response anti–PD-1/PD-L1 therapies. However, the relative diagnostic performance of these modalities has yet be established.

Objective

To compare studies that assessed accuracy IHC, TMB, GEP, mIHC/IF in predicting therapy.

Evidence Review

A search PubMed (from inception June 2018) 2013 2018 annual meeting abstracts from American Association for Cancer Research, Society Clinical Oncology, European Medical Immunotherapy was conducted identify examined use determine objective For only clinical trials resulted US Food Drug Administration approval indications were included. Studies combining more than 1 modality also Preferred Reporting Items Systematic Reviews Meta-analysis guidelines followed. Two reviewers independently extracted outcomes test results each individual study.

Main Outcomes Measures

Summary receiver operating characteristic (sROC) curves; their associated area under curve (AUC); pooled sensitivity, specificity, positive negative predictive values (PPV, NPV), likelihood ratios (LR+ LR−) assay modality.

Results

Tumor specimens representing over 10 different solid types 8135 patients assayed, correlated with response. When evaluated sROC curves, had a significantly higher AUC (0.79) compared IHC (AUC, 0.65,P < .001), GEP = .003), TMB 0.69,P .049). multiple combined such as and/or + drew nearer (0.74). All demonstrated comparable NPV LR−, whereas PPV (0.63) LR+ (2.86) other approaches.

Conclusions Relevance

In this meta-analysis, burden, AUCs treatment. Multiplex immunohistochemistry/IF multimodality biomarker strategies appear improved or alone. Further composite approaches larger number will required confirm findings. Additional study is most analyte combinations whether varies by type.

Language: Английский

Citations

517
Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape DOI Creative Commons

Max D. Wellenstein,

Karin E. de Visser

Immunity, Journal Year: 2018, Volume and Issue: 48(3), P. 399 - 416

Published: March 1, 2018

Language: Английский

Citations

509