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Curr Opin Immunol. 2013 Apr;25(2):200-5. doi: 10.1016/j.coi.2013.01.006. Epub 2013 Feb 17.

Inflammatory networks and immune surveillance of pancreatic carcinoma.

Author information

  • 18-121 Smilow Center for Translational Research, 3400 Civic Center Blvd, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. rhv@exchange.upenn.edu

Abstract

Cancer-associated inflammation plays an important role in restraining anti-tumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA) for which a massive infiltration of immunosuppressive leukocytes into the tumor stroma is an early and consistent event in oncogenesis. Intratumoral effector T cells are rare. This pathophysiology is in contrast to many other solid tumors for which infiltration of effector T cells is often prominent, associated with improved clinical outcomes, and mechanistically contributes to tumor immunoediting that ultimately can mediate immune escape. In PDA, increasing evidence suggests that the ras oncogene drives an inflammatory program that establishes immune privilege in the tumor microenvironment. Indeed, PDA cells might remain intrinsically sensitive to T cell killing because they have never been exposed to T cell selective pressure in vivo. In support of this hypothesis, recent studies demonstrate that derailing immune suppressive pathways in the PDA microenvironment, such as tumor derived GM-CSF, facilitates T-cell mediated tumor rejection. These findings carry major implications for the development of novel, combination immunotherapies for pancreatic cancer.

PMID:
23422836
PMCID:
PMC3647365
DOI:
10.1016/j.coi.2013.01.006
[PubMed - indexed for MEDLINE]
Free PMC Article
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