Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer.
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.
Clark
Carolyn E
CE
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Department of Medicine, 551 BRBII/III, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Beatty
Gregory L
GL
Vonderheide
Robert H
RH
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D019426:Integrases / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017354:Point Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019139:Tumor Escape / Q000235:genetics
C045073:Cre recombinase; D019426:Integrases; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)