Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer

Cancer Lett. 2009 Jun 28;279(1):1-7. doi: 10.1016/j.canlet.2008.09.037. Epub 2008 Nov 14.


The resurgent theory of cancer immunosurveillance holds that the immune system plays an important role in the suppression of tumors, particularly in the elimination of early neoplastic lesions. Tumors with reduced immunogenicity or those that have acquired mechanisms to suppress immune effector functions, however, can emerge from this selection pressure and grow progressively. This is an especially important issue in pancreatic cancer, which although inflammatory in vivo is nevertheless highly aggressive and nearly always lethal. Here, we review emerging data obtained from novel genetically defined mouse models of pancreatic adenocarcinoma that suggest that the immune system may be complicit in the inception and progression of pancreatic cancer. Host immune cells with suppressive properties infiltrate the pancreas early during tumorigenesis, even at the earliest stages of neoplasia, preceding and effectively undermining any lymphocytes with potential antitumor function. Thus, in pancreatic adenocarcinoma, the failure of immunosurveillance is likely an early event during tumorigenesis, a concept that carries important implications for the design of novel immunotherapeutics in this disease.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Disease Progression
  • Integrases / genetics
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Macrophages / immunology
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Myeloid Cells / immunology
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / pathology
  • Point Mutation
  • Proto-Oncogene Proteins p21(ras) / genetics
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Escape* / genetics


  • Cre recombinase
  • Integrases
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)