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EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release
DC Field | Value | Language |
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dc.contributor.author | Suh, Koung Jin | - |
dc.contributor.author | Sung, Ji Hea | - |
dc.contributor.author | Kim, Jin Won | - |
dc.contributor.author | Han, Song-Hee | - |
dc.contributor.author | Lee, Hye Seung | - |
dc.contributor.author | Min, Ahrum | - |
dc.contributor.author | Kang, Mi Hyun | - |
dc.contributor.author | Kim, Ji Eun | - |
dc.contributor.author | Kim, Ji-Won | - |
dc.contributor.author | Kim, Se Hyun | - |
dc.contributor.author | Lee, Jeong-Ok | - |
dc.contributor.author | Kim, Yu Jung | - |
dc.contributor.author | Lee, Keun-Wook | - |
dc.contributor.author | Kim, Jee Hyun | - |
dc.contributor.author | Bang, Soo-Mee | - |
dc.contributor.author | Im, Seock-Ah | - |
dc.contributor.author | Lee, Jong Seok | - |
dc.date.accessioned | 2022-03-22T09:07:12Z | - |
dc.date.available | 2022-03-22T09:07:12Z | - |
dc.date.created | 2018-11-08 | - |
dc.date.created | 2018-11-08 | - |
dc.date.issued | 2017-09 | - |
dc.identifier.citation | Oncotarget, Vol.8 No.38, pp.63901-63910 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.other | 67268 | - |
dc.identifier.uri | https://hdl.handle.net/10371/177161 | - |
dc.description.abstract | Background: Characteristics of tumor microenvironment have been suggested as predictive markers of anti-EGFR or anti-HER2 treatment response. However, the effect of EGFR/HER2 signal blockade on the tumor immune microenvironment is unclear. Methods: EGFR/HER2 pathway signaling and PD-L1 expression in gastric cancer cell lines were screened by western blot analysis. PD-L1 and HER2 expressions in 251 resected gastric tumors were determined by immunohistochemistry, and changes in EFGR, HER2, and PD-L1 expression in paired specimens between pre- and post-chemotherapy were evaluated. PD-L1 expression in HER2-amplified cell lines was evaluated by western blotting, fluorescence-activated cell sorting, reverse transcription, and real-time quantitative PCR analyses before and after afatinib, lapatinib, pictilisib and trametinib treatment. Changes in cytokines were evaluated by reverse transcription, real-time quantitative PCR, and enzyme-linked immunosorbent assay after EGFR/HER2 inhibition. Results: Cell lines with pEGFR or pHER2 overexpression showed higher PD-L1 expression. In resected gastric tumors, HER2 expression was significantly associated with PD-L1 expression (p=0.030). PD-L1 overexpression accompanied by increased HER2 expression was identified in a post-chemotherapy specimen from a patient with an initial HER2/PD-L1-negative tumor. In HER2-overexpressing cell lines, PD-L1 expression was decreased in a dose-and time-dependent manner after afatinib and lapatinib treatment. PI3K pathway inhibition by pictilisib, but not MEK pathway inhibition by trametinib, resulted in PD-L1 suppression. After lapatinib treatment, the release of CCL2, CCL21, VEGF and CXCL1 decreased in a dose-dependent manner. Conclusions: Inhibition of the EGFR/HER2 signaling pathway, particularly of downstream PI3K activity, suppressed PD-L1 and release of cytokines, suggesting that EGFR/HER2 inhibition may create a more favorable milieu for tumor immunotherapy. | - |
dc.language | 영어 | - |
dc.publisher | Impact Journals | - |
dc.title | EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 임석아 | - |
dc.identifier.doi | 10.18632/oncotarget.19194 | - |
dc.citation.journaltitle | Oncotarget | - |
dc.identifier.wosid | 000410284800090 | - |
dc.identifier.scopusid | 2-s2.0-85029810663 | - |
dc.citation.endpage | 63910 | - |
dc.citation.number | 38 | - |
dc.citation.startpage | 63901 | - |
dc.citation.volume | 8 | - |
dc.identifier.sci | 000410284800090 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Lee, Hye Seung | - |
dc.contributor.affiliatedAuthor | Lee, Keun-Wook | - |
dc.contributor.affiliatedAuthor | Kim, Jee Hyun | - |
dc.contributor.affiliatedAuthor | Im, Seock-Ah | - |
dc.contributor.affiliatedAuthor | Lee, Jong Seok | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CELL LUNG-CANCER | - |
dc.subject.keywordPlus | INFILTRATING LYMPHOCYTES | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | NSCLC | - |
dc.subject.keywordAuthor | PD-L1 | - |
dc.subject.keywordAuthor | cytokine | - |
dc.subject.keywordAuthor | EGFR | - |
dc.subject.keywordAuthor | HER2 | - |
dc.subject.keywordAuthor | PI3K | - |
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