Immunosurveillance by T-lymphocytes in pretumoral stages of chemically induced pancreatic carcinogenesis.
Cellular immune-response during pancreatic carcinogenesis induced by N-nitroso-bis(2-hydroxy-propyl)amine in Syrian Golden hamsters was studied using a mouse antiserum to hamster T-lymphocytes in indirect immunofluorescence. The chronology of lesions in this model is, acinar cell atypia, cystadenoma, ductal hyperplasia and adenocarcinoma. Lymphocyte infiltration began before microscopic lesions. Starting as an interstitial and interlobular migration, this earliest population was composed of various kind of mononuclear cells including T-cells. As pancreatic lesions proceeded, an abundant lymphocyte supply through newly formed capillaries (angiogenesis), gave rise to inter- and intralobular nodules composed almost exclusively of T-cells. Migrating from nodules, T-cells invaded and readily destroyed the exocrine tissue. Formation of hyperplasic ducts and of adenocarcinoma was accompanied by considerable accretion of the basal membrane (fibrosis). T-cells were located outside and around this basal membrane so that they never invaded the ductal epithelium. Our results suggest there is an effective immunosurveillance in the early stages of transformation that becomes ineffective at later stages as a consequence of T-cells' inability to pass through the basal membrane barrier surrounding the ductal epithelium in preneoplasic lesions (ductal hyperplasia) and in adenocarcinoma. Extending our observations to human pancreatic cancer could provide a new insight in cellular immunosurveillance and, as a consequence might, help cellular immunotherapeutic approaches for this almost fatal disease.
Ubirajara-Garcia
I
I
Departamento de Microbiologia e Imunologia, Instituto de Biologia, UNICAMP, Campinas, SP, Brazil.
Escribano
M J
MJ
D000818:Animals; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines / Q000633:toxicity; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D009602:Nitrosamines; C012457:diisopropanolnitrosamine