Activated Pancreatic Stellate Cells Sequester CD8+ T Cells to Reduce Their Infiltration of the Juxtatumoral Compartment of Pancreatic Ductal Adenocarcinoma
Abasi Ene–Obong,Andrew Clear,Jennifer Watt,Jennifer Watt,Jun Wang,Rewas Fatah,John Riches,John Marshall,Jo-Anne Chin Aleong,Claude Chelala,John G. Gribben,Alan G. Ramsay,Hemant M. Kocher,Hemant M. Kocher +13 more
TLDR
Based on studies of human PDAC samples and KPC mice, activated PSCs appear to reduce migration of CD8(+) T cells to juxtatumoral stromal compartments, preventing their access to cancer cells.About:
This article is published in Gastroenterology.The article was published on 2013-11-01 and is currently open access. It has received 407 citations till now. The article focuses on the topics: Pancreatic stellate cell & Regulatory T cell.read more
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Journal ArticleDOI
Immunophenotypes of pancreatic ductal adenocarcinoma: Meta-analysis of transcriptional subtypes
Ines de Santiago,Christopher Yau,Lara R. Heij,Lara R. Heij,Mark R. Middleton,Florian Markowetz,Heike I. Grabsch,Heike I. Grabsch,Michael L. Dustin,Michael L. Dustin,Shivan Sivakumar +10 more
TL;DR: An integrative meta‐analysis of 353 patients from four different studies to derive a PDAC classification based on immunologic parameters reveals the existence of microenvironmental interpatient heterogeneity within PDAC and could serve to drive novel therapeutic strategies in PDAC.
Journal ArticleDOI
Effects of Radiation on the Tumor Microenvironment.
Arta M. Monjazeb,Kurt A. Schalper,Franz Villarroel-Espindola,Anthony T. Nguyen,Stephen L. Shiao,Kristina H. Young +5 more
TL;DR: With increased understanding of the effects of RT on the TME, in the future it is likely that the authors will be able to personalize RT by varying the dose, site, and timing of intervention to generate the desired response to partner with immunotherapy strategies.
Journal ArticleDOI
The Extracellular Matrix in Pancreatic Cancer: Description of a Complex Network and Promising Therapeutic Options.
Benedetta Ferrara,Cataldo Pignatelli,Mélissande Cossutta,Antonio Citro,José Courty,Lorenzo Piemonti +5 more
TL;DR: In this article, the authors provide an overview of the principal mechanisms involved in the extracellular matrix remodeling and new promising therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC).
Journal ArticleDOI
Co-targeting of CXCR4 and hedgehog pathways disrupts tumor-stromal crosstalk and improves chemotherapeutic efficacy in pancreatic cancer.
Mohammad Aslam Khan,Sanjeev K. Srivastava,Haseeb Zubair,Girijesh Kumar Patel,Sumit Arora,Moh’d Khushman,James E. Carter,Gregory S. Gorman,Seema Singh,Ajay P. Singh +9 more
TL;DR: It is shown that when PC cells are co-cultured with pancreatic stellate cells (PSCs) they are significantly more resistant to gemcitabine toxicity than those grown in monoculture, and the co-culture–induced chemoresistance is abrogated by inhibition of the CXCR4 and hedgehog pathways.
Journal ArticleDOI
Pancreatic Stellate Cells Promote Tumor Progression by Promoting an Immunosuppressive Microenvironment in Murine Models of Pancreatic Cancer.
Caixia Li,Caixia Li,Lihua Cui,Lihua Cui,Lei Yang,Lei Yang,Botao Wang,Yuzhen Zhuo,Yuzhen Zhuo,Lanqiu Zhang,Lanqiu Zhang,Ximo Wang,Ximo Wang,Qi Zhang,Qi Zhang,Shukun Zhang,Shukun Zhang +16 more
TL;DR: These findings support PSCs playing multiple roles in PDAC development via promoting immunosuppressive microenvironment.
References
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Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome
Jérôme Galon,Anne Costes,Fátima Sánchez-Cabo,Amos Kirilovsky,Bernhard Mlecnik,Christine Lagorce-Pagès,Marie Tosolini,Matthieu Camus,Anne Berger,Philippe Wind,Franck Zinzindohoué,Patrick Bruneval,Paul-Henri Cugnenc,Zlatko Trajanoski,Wolf H. Fridman,Franck Pagès +15 more
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Lin Zhang,Jose R. Conejo-Garcia,Dionyssios Katsaros,Phyllis A. Gimotty,Marco Massobrio,Giorgia Regnani,Antonis Makrigiannakis,Heidi J. Gray,Katia Schlienger,Michael N. Liebman,Stephen C. Rubin,George Coukos +11 more
TL;DR: The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor.
Journal ArticleDOI
Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer
Kenneth P. Olive,Michael A. Jacobetz,Christian Davidson,Aarthi Gopinathan,Aarthi Gopinathan,Dominick J.O. McIntyre,Davina J. Honess,Basetti Madhu,Mae A. Goldgraben,Meredith E. Caldwell,David Allard,Kristopher K. Frese,Gina M. DeNicola,Gina M. DeNicola,Christine Feig,Chelsea Combs,Stephen P. Winter,Heather Ireland-Zecchini,Stefanie Reichelt,William J. Howat,Alex R. Chang,Mousumi Dhara,Lifu Wang,Lifu Wang,Felix Rückert,Robert Grützmann,Christian Pilarsky,Kamel Izeradjene,Sunil R. Hingorani,Pearl S. Huang,Susan E. Davies,William Plunkett,Merrill J. Egorin,Ralph H. Hruban,Nigel Whitebread,Karen McGovern,Julian Adams,Christine A. Iacobuzio-Donahue,John R. Griffiths,David A. Tuveson +39 more
TL;DR: Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, it is found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA.
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