Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy

Frontiers in Bioengineering and Biotechnology
Ben WangYunsheng Ou

Abstract

Background: The recent clinical success of immunotherapy represents a turning point in cancer management. But the response rate of immunotherapy is still limited. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, due to the lack of appropriate experimental methods, the reason why the immunotherapeutic resistance still existed on the inflamed tumor microenvironment remains unclear. Materials and Methods: Here, based on single-cell RNA sequencing, we classified the tumor microenvironment into inflamed immunotherapeutic responsive and inflamed non-responsive. Then, phenotype-specific genes were identified to show mechanistic differences between distant microenvironment phenotypes. Finally, we screened for some potential drugs that can convert an unfavorable microenvironment phenotype to a favorable one to aid current immunotherapy. Results: Multiple signaling pathways were phenotypes-specific dysregulated. Compared to non-inflamed microenvironment, the expression of interleukin signaling pathways-associated genes was upregulated in inflamed microenvironment. Compared to inflamed responsive microenvironment, the PPAR signaling pathway-related genes and multiple epigenetic p...Continue Reading

References

Oct 15, 1989·Annals of Internal Medicine·D H PresentB I Korelitz
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Dec 8, 2011·Cancer Immunology, Immunotherapy : CII·Rui-Ru JiVafa Shahabi
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Jan 18, 2013·BMC Bioinformatics·Sonja HänzelmannJustin Guinney
Apr 9, 2014·International Journal of Cancer. Journal International Du Cancer·Patrick MickeOzlem Türeci
Jan 18, 2015·Cellular Immunology·Guoying NiXiaosong Liu
May 15, 2015·Nature·Stefani SprangerThomas F Gajewski
Jun 2, 2015·The New England Journal of Medicine·James LarkinJedd D Wolchok
Jul 19, 2015·Cancer Letters·Mark H ManninoYujiang Fang
Oct 24, 2015·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Sina HübenerChristoph Schramm
Oct 31, 2015·BMC Bioinformatics·Ivana Ihnatova, Eva Budinska
Dec 15, 2015·Bioinformatics·Petr SmirnovBenjamin Haibe-Kains
Dec 15, 2015·Molecular BioSystems·Guangchuang Yu, Qing-Yu He
Dec 26, 2015·Nucleic Acids Research·Antonio ColapricoHoutan Noushmehr
Apr 20, 2016·JAMA : the Journal of the American Medical Association·Antoni RibasCaroline Robert
Nov 20, 2016·Annual Review of Medicine·Kheng NewickSteven M Albelda
Nov 20, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Adil I DaudOmid Hamid
Jun 7, 2017·Bioinformation·Michael SekulaSusmita Datta
Jun 14, 2017·Cancer Cell·Gabriel Abril-Rodriguez, Antoni Ribas
Jul 30, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chuanbao ZhangAnhua Wu
Dec 2, 2017·Cell·Roderik M KortleverGerard I Evan
Apr 25, 2018·Nature Medicine·Mikhail BinnewiesMatthew F Krummel
Oct 6, 2018·Nucleic Acids Research·Xinxin ZhangYun Xiao
Dec 14, 2018·Experimental & Molecular Medicine·Pramod DarvinEyad Elkord
Jan 6, 2019·Nature Reviews. Drug Discovery·Jérôme Galon, Daniela Bruni
Jun 11, 2019·Cell·Tim StuartRahul Satija
Jan 17, 2020·Nature·Florent PetitprezWolf H Fridman

❮ Previous
Next ❯

Citations

May 25, 2021·Molecular Therapy Oncolytics·Guangshun SunYangbai Sun

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE62944
GSE91061
GSE103322

Software Mentioned

ToPASeq
edgeR package
GSEA
RectomePA
ClusterProfile
optCluster
Seurat
edgeR
PharmacoGx

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here