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Article: Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation

TitleChemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation
Authors
Issue Date2018
PublisherElsevier: Creative Commons Attribution Non-Commercial No-Derivatives License. The Journal's web site is located at http://www.transonc.com
Citation
Translational Oncology, 2018, v. 11, p. 1323-1333 How to Cite?
AbstractThe current study reveals the clinicopathological association of PD-L1 in Hong Kong esophageal squamous cell carcinoma (ESCC) patients and the differential regulation of PD-L1 by standard first-line chemotherapy in ESCC. Immunohistochemical analysis of tissue microarray data from 84 Hong Kong ESCC patients shows that PD-L1 was expressed in 21% of the tumors. Positive PD-L1 staining was significantly associated with later disease stage (stages III and IV) (P value = .0379) and lymph node metastasis (P value = .0466) in the Hong Kong cohort. Furthermore, PD-L1 expression was significantly induced in ESCC cell lines after standard chemotherapy treatments, along with EGFR and ERK activation in both in vitro studies and the in vivo esophageal orthotopic model. The endogenous expression of PD-L1 was reduced by treatment with an EGFR inhibitor (erlotinib) or by the knockdown of EGFR. Moreover, the upregulation of PD-L1 by chemotherapy was also attenuated by the treatment with erlotinib and a MAPK/MEK inhibitor (AZD6244), suggesting that PD-L1 is regulated by the EGFR/ERK pathway in ESCC. The regulation of PD-L1 by the EGFR pathway was further supported by the correlation of PD-L1 and EGFR expression observed in the commercially available tissue microarray set (P value = .028). Taken together, the current study was the first to demonstrate the upregulation of PD-L1 by chemotherapy in ESCC and its regulation through the EGFR/ERK pathway. The results suggest the potential usefulness of combined conventional chemotherapy together with anti–PD-L1 immunotherapy to achieve better treatment outcome.
Persistent Identifierhttp://hdl.handle.net/10722/261113
ISSN
2015 Impact Factor: 3.077
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNg, HY-
dc.contributor.authorLI, J-
dc.contributor.authorTao, L-
dc.contributor.authorLam, AK-
dc.contributor.authorChan, KW-
dc.contributor.authorKo, JMY-
dc.contributor.authorYu, Z-
dc.contributor.authorWong, M-
dc.contributor.authorLi, B-
dc.contributor.authorLung, ML-
dc.date.accessioned2018-09-14T08:52:44Z-
dc.date.available2018-09-14T08:52:44Z-
dc.date.issued2018-
dc.identifier.citationTranslational Oncology, 2018, v. 11, p. 1323-1333-
dc.identifier.issn1944-7124-
dc.identifier.urihttp://hdl.handle.net/10722/261113-
dc.description.abstractThe current study reveals the clinicopathological association of PD-L1 in Hong Kong esophageal squamous cell carcinoma (ESCC) patients and the differential regulation of PD-L1 by standard first-line chemotherapy in ESCC. Immunohistochemical analysis of tissue microarray data from 84 Hong Kong ESCC patients shows that PD-L1 was expressed in 21% of the tumors. Positive PD-L1 staining was significantly associated with later disease stage (stages III and IV) (P value = .0379) and lymph node metastasis (P value = .0466) in the Hong Kong cohort. Furthermore, PD-L1 expression was significantly induced in ESCC cell lines after standard chemotherapy treatments, along with EGFR and ERK activation in both in vitro studies and the in vivo esophageal orthotopic model. The endogenous expression of PD-L1 was reduced by treatment with an EGFR inhibitor (erlotinib) or by the knockdown of EGFR. Moreover, the upregulation of PD-L1 by chemotherapy was also attenuated by the treatment with erlotinib and a MAPK/MEK inhibitor (AZD6244), suggesting that PD-L1 is regulated by the EGFR/ERK pathway in ESCC. The regulation of PD-L1 by the EGFR pathway was further supported by the correlation of PD-L1 and EGFR expression observed in the commercially available tissue microarray set (P value = .028). Taken together, the current study was the first to demonstrate the upregulation of PD-L1 by chemotherapy in ESCC and its regulation through the EGFR/ERK pathway. The results suggest the potential usefulness of combined conventional chemotherapy together with anti–PD-L1 immunotherapy to achieve better treatment outcome.-
dc.languageeng-
dc.publisherElsevier: Creative Commons Attribution Non-Commercial No-Derivatives License. The Journal's web site is located at http://www.transonc.com-
dc.relation.ispartofTranslational Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleChemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation-
dc.typeArticle-
dc.identifier.emailNg, HY: hyng0812@hku.hk-
dc.identifier.emailTao, L: taolihua@hku.hk-
dc.identifier.emailChan, KW: kwchan@pathology.hku.hk-
dc.identifier.emailKo, JMY: joko@hku.hk-
dc.identifier.emailYu, Z: zvyu@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityChan, KW=rp00330-
dc.identifier.authorityKo, JMY=rp02011-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.tranon.2018.08.005-
dc.identifier.hkuros290197-
dc.identifier.volume11-
dc.identifier.spage1323-
dc.identifier.epage1333-
dc.identifier.isiWOS:000445096500006-
dc.publisher.placeUnited States-

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