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Article: PD-L1 expression is a prognostic factor in subgroups of gastric cancer patients stratified according to their levels of CD8 and FOXP3 immune markers

TitlePD-L1 expression is a prognostic factor in subgroups of gastric cancer patients stratified according to their levels of CD8 and FOXP3 immune markers
Authors
KeywordsClustering analysis
gastric cancer
multiplexed immunohistochemistry
prognostic
Issue Date2018
PublisherTaylor & Francis Inc. The Journal's web site is located at http://www.tandfonline.com/koni
Citation
OncoImmunology, 2018, v. 7, p. e1433520 How to Cite?
AbstractCurrent studies aiming at identifying single immune markers with prognostic value have limitations in the context of complex antitumor immunity and cancer immune evasion. Here, we show how the integration of several immune markers influences the predictions of prognosis of gastric cancer (GC) patients. We analyzed Tissue Microarray (TMA) by multiplex immunohistochemistry and measured the expression of immune checkpoint molecule PD-L1 together with antitumor CD8 T cells and immune suppressive FOXP3 Treg cells in a cohort of GC patients. Unsupervised hierarchical clustering analysis of these markers was used to define correlations between CD8 T, FOXP3 Treg and PD-L1 cell densities. We found that FOXP3 and PD-L1 densities were elevated while CD8 T cells were decreased in tumor tissues compared to their adjacent normal tissues. However, patient stratification based on each one of these markers individually did not show significant prognostic value on patient survival. Conversely, combination of the ratios of CD8/FOXP3 and CD8/PD-L1 enabled the identification of patient subgroups with different survival outcomes. As such, high densities of PD-L1 in patients with high CD8/FOXP3 and low CD8/PD-L1 ratios correlated with increased survival. Collectively, this work demonstrates the need for the integration of several immune markers to obtain more meaningful survival prognosis and patient stratification. In addition, our work provides insights into the complex tumor immune evasion and immune regulation by the tumor-infiltrating effector and suppressor cells, informing on the best use of immunotherapy options for treating patients.
Persistent Identifierhttp://hdl.handle.net/10722/251572
ISSN
2017 Impact Factor: 5.503
2015 SCImago Journal Rankings: 1.485
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYing, L-
dc.contributor.authorYan, F-
dc.contributor.authorMeng, Q-
dc.contributor.authorYu, L-
dc.contributor.authorYuan, X-
dc.contributor.authorGantier, MP-
dc.contributor.authorWilliams, BR-
dc.contributor.authorChan, DW-
dc.contributor.authorShi, L-
dc.contributor.authorTu, Y-
dc.contributor.authorNi, P-
dc.contributor.authorWang, X-
dc.contributor.authorChen, W-
dc.contributor.authorZang, X-
dc.contributor.authorXu, D-
dc.contributor.authorHu, Y-
dc.date.accessioned2018-03-02T08:17:58Z-
dc.date.available2018-03-02T08:17:58Z-
dc.date.issued2018-
dc.identifier.citationOncoImmunology, 2018, v. 7, p. e1433520-
dc.identifier.issn2162-402X-
dc.identifier.urihttp://hdl.handle.net/10722/251572-
dc.description.abstractCurrent studies aiming at identifying single immune markers with prognostic value have limitations in the context of complex antitumor immunity and cancer immune evasion. Here, we show how the integration of several immune markers influences the predictions of prognosis of gastric cancer (GC) patients. We analyzed Tissue Microarray (TMA) by multiplex immunohistochemistry and measured the expression of immune checkpoint molecule PD-L1 together with antitumor CD8 T cells and immune suppressive FOXP3 Treg cells in a cohort of GC patients. Unsupervised hierarchical clustering analysis of these markers was used to define correlations between CD8 T, FOXP3 Treg and PD-L1 cell densities. We found that FOXP3 and PD-L1 densities were elevated while CD8 T cells were decreased in tumor tissues compared to their adjacent normal tissues. However, patient stratification based on each one of these markers individually did not show significant prognostic value on patient survival. Conversely, combination of the ratios of CD8/FOXP3 and CD8/PD-L1 enabled the identification of patient subgroups with different survival outcomes. As such, high densities of PD-L1 in patients with high CD8/FOXP3 and low CD8/PD-L1 ratios correlated with increased survival. Collectively, this work demonstrates the need for the integration of several immune markers to obtain more meaningful survival prognosis and patient stratification. In addition, our work provides insights into the complex tumor immune evasion and immune regulation by the tumor-infiltrating effector and suppressor cells, informing on the best use of immunotherapy options for treating patients.-
dc.languageeng-
dc.publisherTaylor & Francis Inc. The Journal's web site is located at http://www.tandfonline.com/koni-
dc.relation.ispartofOncoImmunology-
dc.rightsThis is an electronic version of an article published in [include the complete citation information for the final version of the article as published in the print edition of the journal]. [JOURNAL TITLE] is available online at: http://www.informaworld.com/smpp/ with the open URL of your article.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectClustering analysis-
dc.subjectgastric cancer-
dc.subjectmultiplexed immunohistochemistry-
dc.subjectprognostic-
dc.titlePD-L1 expression is a prognostic factor in subgroups of gastric cancer patients stratified according to their levels of CD8 and FOXP3 immune markers-
dc.typeArticle-
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.authorityChan, DW=rp00543-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1080/2162402X.2018.1433520-
dc.identifier.hkuros284378-
dc.identifier.volume7-
dc.identifier.spagee1433520-
dc.identifier.epagee1433520-
dc.identifier.isiWOS:000432214900016-
dc.publisher.placeUnited States-

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