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The tumor microenvironment of pancreatic adenocarcinoma and immune checkpoint inhibitor resistance: a perplex relationship

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Cancer Drug Resistance 2020年第4期3卷 699-709页

作者： Irem Sahin Sevda Turen Pranav Santapuram Ibrahim Halil Sahin Baskent University School of Medicine Department of Medicine AnkaraAnkara 06810Turkey TC Istanbul Kültür University Faculty of Health SciencesDepartment of NursingIstanbul 34158Turkey Emory University School of Medicine Department of MedicineAtlantaGA 30322USA Moffitt Cancer Center Department of Gastrointestinal OncologyTampaFL 33612USA

Pancreatic cancer is one of the most aggressive cancers with a high mortality rate even among patients with early-stage *** recent studies with novel therapeutic approaches have led to modest improvement in survival outcomes,limited progress is achieved for the use of immunotherapeutics in this challenging *** checkpoint inhibitors,thus far,single-agent or in combination,have not yielded significant improvement in survival outcomes except in mismatch repair-deficient pancreatic *** tumor microenvironment of pancreatic cancer has been considered as an attractive target for over a decade based on preclinical studies that suggested it may adversely affect drug delivery and antitumor *** this review article,we elaborate on the biology of pancreatic cancer microenvironment,its highly complicated interaction with cancer cells,and the immune *** also discuss plausible explanations that led to the failure of immune checkpoint inhibitors as therapeutic agents and the potential impacts of pancreatic cancer stroma on these negative studies.

关键词： Pancreatic adenocarcinoma durvalumab nivolumab ipilimumab pembrolizumab immune checkpoint inhibitors immunotherapy resistance mismatch repair deficient microsatellite instability high microsatellite stable tumor-associated macrophages myeloid-derived suppressor cells T regs T cells

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