Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.

The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor fr...

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Autores principales:	Keller J Toral, Mark A Wuenschel, Esther P Black
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d7801d876b04b58a06872bac8a15f68
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spelling	oai:doaj.org-article:9d7801d876b04b58a06872bac8a15f682021-12-02T20:19:32ZGenomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.1932-620310.1371/journal.pone.0256416https://doaj.org/article/9d7801d876b04b58a06872bac8a15f682021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256416https://doaj.org/toc/1932-6203The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor from the immune system of a patient. However, despite accounts of significant tumor regression resulting from these medications, most patients do not respond. In this study, we sought to use protein expression and RNA sequencing data from The Cancer Genome Atlas and two smaller studies deposited onto the Gene Expression Omnibus (GEO) to advance our hypothesis that inhibition of SHP-2, a tyrosine phosphatase, will improve the activity of immune checkpoint inhibitors (ICI) that target PD-1 or PD-L1 in lung cancers. We first collected protein expression data from The Cancer Proteome Atlas (TCPA) to study the association of SHP-2 and PD-L1 expression in lung adenocarcinomas. RNA sequencing data was collected from the same subjects through the NCI Genetic Data Commons and evaluated for expression of the PTPN11 (SHP-2) and CD274 (PD-L1) genes. We then analyzed RNA sequencing data from a series of melanoma patients who were either treatment naïve or resistant to ICI therapy. PTPN11 and CD274 expression was compared between groups. Finally, we analyzed gene expression and drug response data collected from 21 non-small cell lung cancer (NSCLC) patients for PTPN11 and CD274 expression. From the three studies, we hypothesize that the activity of SHP-2, rather than the expression, likely controls the expression of PD-L1 as only a weak relationship between PTPN11 and CD274 expression in either lung adenocarcinomas or melanomas was observed. Lastly, the expression of CD274, not PTPN11, correlates with response to ICI in NSCLC.Keller J ToralMark A WuenschelEsther P BlackPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256416 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keller J Toral Mark A Wuenschel Esther P Black Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.
description	The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor from the immune system of a patient. However, despite accounts of significant tumor regression resulting from these medications, most patients do not respond. In this study, we sought to use protein expression and RNA sequencing data from The Cancer Genome Atlas and two smaller studies deposited onto the Gene Expression Omnibus (GEO) to advance our hypothesis that inhibition of SHP-2, a tyrosine phosphatase, will improve the activity of immune checkpoint inhibitors (ICI) that target PD-1 or PD-L1 in lung cancers. We first collected protein expression data from The Cancer Proteome Atlas (TCPA) to study the association of SHP-2 and PD-L1 expression in lung adenocarcinomas. RNA sequencing data was collected from the same subjects through the NCI Genetic Data Commons and evaluated for expression of the PTPN11 (SHP-2) and CD274 (PD-L1) genes. We then analyzed RNA sequencing data from a series of melanoma patients who were either treatment naïve or resistant to ICI therapy. PTPN11 and CD274 expression was compared between groups. Finally, we analyzed gene expression and drug response data collected from 21 non-small cell lung cancer (NSCLC) patients for PTPN11 and CD274 expression. From the three studies, we hypothesize that the activity of SHP-2, rather than the expression, likely controls the expression of PD-L1 as only a weak relationship between PTPN11 and CD274 expression in either lung adenocarcinomas or melanomas was observed. Lastly, the expression of CD274, not PTPN11, correlates with response to ICI in NSCLC.
format	article
author	Keller J Toral Mark A Wuenschel Esther P Black
author_facet	Keller J Toral Mark A Wuenschel Esther P Black
author_sort	Keller J Toral
title	Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.
title_short	Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.
title_full	Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.
title_fullStr	Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.
title_full_unstemmed	Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.
title_sort	genomic data from nsclc tumors reveals correlation between shp-2 activity and pd-l1 expression and suggests synergy in combining shp-2 and pd-1/pd-l1 inhibitors.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9d7801d876b04b58a06872bac8a15f68
work_keys_str_mv	AT kellerjtoral genomicdatafromnsclctumorsrevealscorrelationbetweenshp2activityandpdl1expressionandsuggestssynergyincombiningshp2andpd1pdl1inhibitors AT markawuenschel genomicdatafromnsclctumorsrevealscorrelationbetweenshp2activityandpdl1expressionandsuggestssynergyincombiningshp2andpd1pdl1inhibitors AT estherpblack genomicdatafromnsclctumorsrevealscorrelationbetweenshp2activityandpdl1expressionandsuggestssynergyincombiningshp2andpd1pdl1inhibitors
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Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.

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