Blockade of CCL2 expression overcomes intrinsic PD-1/PD-L1 inhibitor-resistance in transglutaminase 2-induced PD-L1 positive triple negative breast cancer
DC Field | Value | Language |
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dc.contributor.author | Choi, Junyoung | - |
dc.contributor.author | Lee, Hee Jin | - |
dc.contributor.author | Yoon, Shinkyo | - |
dc.contributor.author | Ryu, Hyun-Min | - |
dc.contributor.author | Lee, Eunjin | - |
dc.contributor.author | Jo, Yujin | - |
dc.contributor.author | Seo, Seyoung | - |
dc.contributor.author | Kim, Deokhoon | - |
dc.contributor.author | Lee, Chang Hoon | - |
dc.contributor.author | Kim, Wanlim | - |
dc.contributor.author | Ha, Joo Young | - |
dc.contributor.author | Kim, Soo-Youl | - |
dc.contributor.author | Gong, Gyungyub | - |
dc.contributor.author | Jung, Kyung Hae | - |
dc.contributor.author | Park, Sook Ryun | - |
dc.contributor.author | Kim, Sang-We | - |
dc.contributor.author | Park, Kang-Seo | - |
dc.contributor.author | Lee, Dae Ho | - |
dc.date.accessioned | 2023-03-08T14:52:45Z | - |
dc.date.available | 2023-03-08T14:52:45Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 2156-6976 | - |
dc.identifier.issn | 2156-6976 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/63619 | - |
dc.description.abstract | Anti-PD-1/PD-L1 immunotherapy, as a treatment for many tumors, has shown good efficacy. However, responses to immunotherapy did not always occur or last long., i.e. primary or acquired resistance, even tumors were PD-L1 positive. Several oncogenic pathways, including PI3K/AKT activation by PTEN loss and NF-kappa B activation, induce PD-L1 expression and PD-L1 inhibitor-resistance. They also induce expression of CCL2, an inhibitory chemokine that blocks T cell tracking into the tumor by binding to CCR2 on the T cell surface. In this study, we showed that transglutaminase 2 (TG2), a post-translational modification enzyme, induced ubiquitin-proteasome dependent degradation of tumor suppressors including PTEN and I kappa B alpha by peptide cross-linking, inducing CCL2 as well as PD-L1 expression via PI3K/AKT and NF-kappa B activation. It also induced PD-L1 inhibitor-resistance because CCL2 was expressed despite increased PD-L1, which was blocked by PD-L1 inhibitor. We also revealed that inhibition of TG2, instead of PD-L1, restored T cell-dependent killing effect by blocking expression of both PD-L1 and CCL2 in PD-L1(+) triple negative breast cancer (TNBC) cells. In addition, the TG2-expressingTN BC patient group showed higher PD-L1 expression incidence than did the TG2-negative TNBC patient group. In conclusion, TG2 induces primary PD-1/PD-L1 inhibitor-resistance by inducing CCL2 expression. TG2 blockade can be utilized as an excellent therapeutic strategy to overcome PD-L1 inhibitor-resistance in PD-L1(+) TNBC patients. Our study suggested that PD-L1 expression alone might not always be a predictive biomarker for PD-L1(+)TNBC, but TG2 could be a useful predictive marker to select PD-L1 inhibitor-resistant TNBC patients. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | E-CENTURY PUBLISHING CORP | - |
dc.title | Blockade of CCL2 expression overcomes intrinsic PD-1/PD-L1 inhibitor-resistance in transglutaminase 2-induced PD-L1 positive triple negative breast cancer | - |
dc.type | Article | - |
dc.identifier.bibliographicCitation | AMERICAN JOURNAL OF CANCER RESEARCH, v.10, no.9, pp 2878 - + | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000579459200013 | - |
dc.citation.endPage | + | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 2878 | - |
dc.citation.title | AMERICAN JOURNAL OF CANCER RESEARCH | - |
dc.citation.volume | 10 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | Transglutaminase 2 | - |
dc.subject.keywordAuthor | TNBC | - |
dc.subject.keywordAuthor | PD-1 | - |
dc.subject.keywordAuthor | PD-L1 | - |
dc.subject.keywordAuthor | drug resistance | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | OPEN-LABEL | - |
dc.subject.keywordPlus | PEMBROLIZUMAB | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordPlus | RECRUITMENT | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | CELLS | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
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