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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NetrinG1/NGL-1 Axis promotes pancreatic tumorigenesis through cancer associated fibroblast derived nutritional supply and immunosuppression
Ralph Francescone,Débora Barbosa Vendramini-Costa,Janusz Franco-Barraza,Jessica Wagner,Alexander Muir,Linara Gabitova,Tatiana Pazina,Tiffany Luong,Neelima Shah,Dustin Rollins,Ruchi Malik,Sapna Gupta,Roshan J. Thapa,Diana Restifo,Allison N. Lau,Yan Zhou,Kathy Q. Cai,Harvey Hensley,Emmanuelle Nicolas,Warren D. Kruger,Karthik Devarajan,Siddharth Balachandran,Wafik S. El-Deiry,Matthew Vander Heiden,Kerry S. Campbell,Igor Astsaturov,Edna Cukierman +26 more
TL;DR: The results helped clarify the role that CAFs play in PDAC, by defining CAF phenotypes through NetG1 expression, and established a link between CAF driven metabolism and their intrinsic immunosuppressive capacity, and identified a signaling circuit that governs netG1 functions.
Journal ArticleDOI
The vitamin D analogue calcipotriol promotes an anti-tumorigenic phenotype of human pancreatic CAFs but reduces T cell mediated immunity.
Laia Gorchs,Sultan Ahmed,Chanté Mayer,Alisa Knauf,Carlos Fernández Moro,Carlos Fernández Moro,Mattias Svensson,Rainer Heuchel,Elena Rangelova,Elena Rangelova,Peter Bergman,Peter Bergman,Helen Kaipe,Helen Kaipe +13 more
TL;DR: It is found that calcipotriol reduces the tumour supportive activity of CAFs but at the same time reduces T cell effector functions, which could compromise the patients’ tumour immune surveillance.
Journal ArticleDOI
Pancreatic cancer-derived exosomes induce apoptosis of T lymphocytes through the p38 MAPK-mediated endoplasmic reticulum stress.
Tao Shen,Zihang Huang,Chengfei Shi,Xiaofan Pu,Xiaodong Xu,Zhengrong Wu,Guoping Ding,Liping Cao,Liping Cao +8 more
TL;DR: Results indicate that pancreatic cancer cells secrete exosomes, which are taken up by T lymphocytes to activate p38 MAPK, and then induce ER stress‐mediated apoptosis, ultimately causing immunosuppression.
Journal ArticleDOI
Lactate transporters as therapeutic targets in cancer and inflammatory diseases.
TL;DR: The therapeutic potential of targeting lactate transporters and drugs that are already in clinical use for cancer and the opportunity to develop new therapeutics for inflammation and cancer are discussed.
Journal ArticleDOI
New avenues for improving pancreatic ductal adenocarcinoma (PDAC) treatment: Selective stroma depletion combined with nano drug delivery.
TL;DR: The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell, so disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC.
References
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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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