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

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 checkp...

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Autores principales: Gaffney, Stephen G., Perry, Elizabeth B., Chen, Ping-Min, Greenstein, Andrew, Kaech, Susan M., Townsend, Jeffrey P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642048/
https://www.ncbi.nlm.nih.gov/pubmed/31360302
http://dx.doi.org/10.18632/oncotarget.27027
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author Gaffney, Stephen G.
Perry, Elizabeth B.
Chen, Ping-Min
Greenstein, Andrew
Kaech, Susan M.
Townsend, Jeffrey P.
author_facet Gaffney, Stephen G.
Perry, Elizabeth B.
Chen, Ping-Min
Greenstein, Andrew
Kaech, Susan M.
Townsend, Jeffrey P.
author_sort Gaffney, Stephen G.
collection PubMed
description 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 high CD3E co-expression and relatively low PDCD1 co-expression.
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spelling pubmed-66420482019-07-29 The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment Gaffney, Stephen G. Perry, Elizabeth B. Chen, Ping-Min Greenstein, Andrew Kaech, Susan M. Townsend, Jeffrey P. Oncotarget Research Paper 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 high CD3E co-expression and relatively low PDCD1 co-expression. Impact Journals LLC 2019-07-16 /pmc/articles/PMC6642048/ /pubmed/31360302 http://dx.doi.org/10.18632/oncotarget.27027 Text en Copyright: © 2019 Gaffney et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Gaffney, Stephen G.
Perry, Elizabeth B.
Chen, Ping-Min
Greenstein, Andrew
Kaech, Susan M.
Townsend, Jeffrey P.
The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment
title The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment
title_full The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment
title_fullStr The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment
title_full_unstemmed The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment
title_short The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment
title_sort landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642048/
https://www.ncbi.nlm.nih.gov/pubmed/31360302
http://dx.doi.org/10.18632/oncotarget.27027
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