Stromal protein beta ig-h3 reprogrammes tumour microenvironment in pancreatic cancer
DC Field | Value | Language |
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dc.contributor.author | Goehrig, Delphine | - |
dc.contributor.author | Nigri, Jeremy | - |
dc.contributor.author | Samain, Remi | - |
dc.contributor.author | Wu, Zhichong | - |
dc.contributor.author | Cappello, Paola | - |
dc.contributor.author | Gabiane, Gaelle | - |
dc.contributor.author | Zhang, Xinyi | - |
dc.contributor.author | Zhao, Yajie | - |
dc.contributor.author | Kim, In-San | - |
dc.contributor.author | Chanal, Marie | - |
dc.contributor.author | Curto, Roberta | - |
dc.contributor.author | Hervieu, Valerie | - |
dc.contributor.author | de La Fouchardiere, Christelle | - |
dc.contributor.author | Novelli, Francesco | - |
dc.contributor.author | Milani, Pascale | - |
dc.contributor.author | Tomasini, Richard | - |
dc.contributor.author | Bousquet, Corinne | - |
dc.contributor.author | Bertolino, Philippe | - |
dc.contributor.author | Hennino, Ana | - |
dc.date.accessioned | 2021-09-01T17:03:43Z | - |
dc.date.available | 2021-09-01T17:03:43Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2019-04 | - |
dc.identifier.issn | 0017-5749 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/66520 | - |
dc.description.abstract | Objective Pancreatic cancer is associated with an abundant stromal reaction leading to immune escape and tumour growth. This massive stroma drives the immune escape in the tumour. We aimed to study the impact of beta ig-h3 stromal protein in the modulation of the antitumoural immune response in pancreatic cancer. Design We performed studies with p48-Cre;Kras(G12D), pdx1-Cre;Kras(G12D); Ink4a/Ar-ffl/fl, pdx1-Cre; Kras(G12D); p53(R172H) mice and tumour tissues from patients with pancreatic ductal adenocarcinoma (PDA). Some transgenic mice were given injections of anti-beta ig-h3, anti-CD8, anti-PD1 depleting antibodies. Tumour growth as well as modifications in the activation of local immune cells were analysed by flow cytometry, immunohistochemistry and immunofluorescence. Tissue stiffness was measured by atomic force microscopy. Results We identified beta ig-h3 stromal-derived protein as a key actor of the immune paracrine interaction mechanism that drives pancreatic cancer. We found that beta ig-h3 is highly produced by cancer-associated fibroblasts in the stroma of human and mouse. This protein acts directly on tumour-specific CD8(+) T cells and F4/80 macrophages. Depleting beta ig-h3 in vivo reduced tumour growth by enhancing the number of activated CD8(+) T cell within the tumour and subsequent apoptotic tumour cells. Furthermore, we found that targeting beta ig-h3 in established lesions released the tissue tension and functionally reprogrammed F4/80 macrophages in the tumour microenvironment. Conclusions Our data indicate that targeting stromal extracellular matrix protein beta ig-h3 improves the antitumoural response and consequently reduces tumour weight. Our findings present beta ig-h3 as a novel immunological target in pancreatic cancer. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BMJ PUBLISHING GROUP | - |
dc.subject | GROWTH-FACTOR-BETA | - |
dc.subject | DUCTAL ADENOCARCINOMA | - |
dc.subject | T-CELLS | - |
dc.subject | IDENTIFICATION | - |
dc.subject | ADHESION | - |
dc.subject | EXPRESSION | - |
dc.subject | INFLAMMATION | - |
dc.subject | DYSFUNCTION | - |
dc.subject | FIBROBLASTS | - |
dc.subject | COOPERATE | - |
dc.title | Stromal protein beta ig-h3 reprogrammes tumour microenvironment in pancreatic cancer | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, In-San | - |
dc.identifier.doi | 10.1136/gutjnl-2018-317570 | - |
dc.identifier.scopusid | 2-s2.0-85056382560 | - |
dc.identifier.wosid | 000471830300015 | - |
dc.identifier.bibliographicCitation | GUT, v.68, no.4, pp.693 - 707 | - |
dc.relation.isPartOf | GUT | - |
dc.citation.title | GUT | - |
dc.citation.volume | 68 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 693 | - |
dc.citation.endPage | 707 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Gastroenterology & Hepatology | - |
dc.relation.journalWebOfScienceCategory | Gastroenterology & Hepatology | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | DUCTAL ADENOCARCINOMA | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | ADHESION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | DYSFUNCTION | - |
dc.subject.keywordPlus | FIBROBLASTS | - |
dc.subject.keywordPlus | COOPERATE | - |
dc.subject.keywordAuthor | immune response | - |
dc.subject.keywordAuthor | pancreatic cancer | - |
dc.subject.keywordAuthor | t lymphocytes | - |
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