The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment

Oncotarget
Stephen G GaffneyJeffrey P Townsend

Abstract

Background: Immunotherapies targeting immune checkpoint proteins CTLA-4, PD-1, and PD-L1 have saved lives, but these therapies have only been effective in some patients. Patients positive for expression of immune checkpoint proteins in the tumor microenvironment show better response to immune checkpoint inhibitors. Consequently, knowledge of which genes are consistently expressed in lymphocytes within the tumor microenvironment can convey potentially effective and complementary new immunotherapy targets. Results: We identified 54 genes that have higher co-expression with the pan T-cell marker CD3E than CTLA4 or PDCD1. In a dataset of 26 patients who received anti-PD-1 therapy, we observed that co-expression between CD3E and PDCD1 was higher among responders than non-responders, supporting our correlation-based approach. Conclusions: The genes highlighted in these analyses, which include CD6, TIGIT, CD96, and SLAMF6, warrant further investigation of their therapeutic potential. Methods: We analyzed and ranked genes that were co-expressed with the pan T-cell marker CD3E in 9,601 human tumors, spanning 31 cancer types. To further identify targets that may be complementary to existing PD-1 therapy, we examined and ranked genes with...Continue Reading

References

Aug 1, 1994·The Journal of Pathology·R Chetty, K Gatter
Feb 28, 2004·The Journal of Biological Chemistry·Patricia A ValdezIqbal S Grewal
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Dec 24, 2005·The New England Journal of Medicine·Franck PagèsJérôme Galon
Mar 1, 2007·Blood·Ainhoa Perez-DiezPolly Matzinger
Oct 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Noa StanietskyOfer Mandelboim
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Mar 15, 2011·Critical Reviews in Immunology·Vibhuti P Dave
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Mar 23, 2012·Nature Reviews. Immunology·Nicholas P RestifoSteven A Rosenberg
Sep 19, 2012·Cancer Immunology, Immunotherapy : CII·Pornpimol CharoentongZlatko Trajanoski
Dec 1, 2012·Genome Medicine·Matthias Schwab, Elke Schaeffeler
Dec 18, 2012·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Sine HadrupPer Thor Straten
Feb 2, 2013·Nature Reviews. Drug Discovery·Sheng YaoLieping Chen
Feb 6, 2013·Cytokine & Growth Factor Reviews·Simone MocellinPierluigi Pilati
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Sep 21, 2013·Nature·Rebecca A BurrellCharles Swanton
Sep 26, 2013·Nature Reviews. Cancer·Caitriona HolohanPatrick G Johnston
Oct 12, 2013·The Journal of Pathology·Brian G BlairBen Ho Park
Mar 22, 2014·Cancer Biology & Therapy·Martina SanlorenzoSusanna Ortiz-Urda
Jun 7, 2014·Molecular Cell·Hariharan EaswaranStephen B Baylin
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertPaolo A Ascierto
Jan 31, 2015·Archives of Pharmacal Research·Inkyu Hwang, Nguyet Nguyen
Feb 25, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maurizio Zanetti
Mar 10, 2015·Molecular Immunology·Abhisek SwaikaRichard W Joseph
Mar 31, 2015·Seminars in Cancer Biology·Dass S VinayByoung S Kwon
May 7, 2015·Clinical, Cosmetic and Investigational Dermatology·Roshni Menon, Brinda G David
Aug 1, 2015·Nature Reviews. Drug Discovery·Kathleen M MahoneyGordon J Freeman
Sep 26, 2015·The New England Journal of Medicine·Robert J MotzerUNKNOWN CheckMate 025 Investigators
Sep 29, 2015·The Journal of Clinical Investigation·Sema KurtulusAna C Anderson
Jan 23, 2016·Current Opinion in Immunology·Federico GarridoThorbald van Hall
Apr 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Priti S HegdeStefan Evers
Aug 28, 2016·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Kazuhiko ShienIgnacio I Wistuba
Nov 3, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephen J BlakeMark J Smyth

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Citations

Mar 23, 2021·Frontiers in Molecular Biosciences·Zhihua ZuoYongcan Guo
Aug 9, 2021·Progress in Biophysics and Molecular Biology·Krishna DasariJeffrey P Townsend

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Methods Mentioned

BETA
RNA-Seq
biopsies

Software Mentioned

Python
GSEA
cBio Cancer Genomics Portal
irRECIST
numpy
statsmodels
RSEM

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