Quiescent tumor cells shape the immunosuppressive microenvironment in pancreatic ductal adenocarcinoma

Quiescent tumor cells shape the immunosuppressive microenvironment in pancreatic ductal adenocarcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Quiescent tumor cells shape the immunosuppressive microenvironment in pancreatic ductal adenocarcinoma William Matsui, Bryan McClellan, Qiuju Wang, Kyaw Aung This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8980750/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Immunotherapy, including chimeric antigen receptor (CAR) T-cell therapy, has limited activity in pancreatic ductal adenocarcinoma (PDAC). Using orthotopic PDAC mouse models, we identified a rare population of quiescent PDAC cells that increases after CAR-T cell therapy and exhibits relatively higher clonogenic growth and self-renewal potential than bulk tumor cells. These quiescent cells express high levels of Epiregulin (EREG), a secreted ligand for EGFR and ErbB4, and induce an immunosuppressive tumor microenvironment by increasing the frequency of ErbB4-expressing tumor-associated macrophages. Silencing EREG expression increased the sensitivity of both quiescent cells and tumors to CAR-T cells and improved relapse rates and overall survival. These findings demonstrate that rare quiescent tumor cells can modulate the tumor microenvironment in PDAC and suggest that EREG inhibition may enhance the efficacy of adoptive immunotherapeutic approaches in this disease. Biological sciences/Cancer/Cancer microenvironment Biological sciences/Cancer/Tumour immunology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files PDXCharacterisitcs.xlsx Patient derived tissue characteristics DifferentiallyexpressedgenesmVenusNegativevsmVenusHigh.xlsx Differentially gene expression p27k-mVenus Negative vs High Flowcytometrygatingandfullwesternblots.pdf Gating Strategy and full western blot images supplemenatrymaterialstable.xlsx Supplementary Materials Table Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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