title: Inflammatory cell infiltrate associated with primary and transplanted tumours in an inbred model of oral carcinogenesis.
abstract: This study characterised the nature of the local cellular immune responses associated with an inbred animal model of oral carcinogenesis. Inbred F344 rats developed moderately- to well-differentiated primary oral squamous cell carcinomas (SCC) after treatment with the carcinogen 4-nitroquinoline N-oxide (4-NQO) in vivo for 5-6 months. The inflammatory cell infiltrate associated with the primary tumours was predominantly of the macrophage lineage (CD45+, Ia+) and contained smaller numbers of CD8+ cells (NK cells, cytotoxic/suppressor T cells), CD5+ cells (T cells) and CD25+ cells (activated cells; T and NK cells). Keratinocyte cell lines were established from three lingual and one palatal SCC. By contrast to normal keratinocytes, tumour-derived cell lines were immortal and independent of 3T3 fibroblast support. All of the tumour-derived cell lines were tumorigenic in athymic (nu/nu) mice and showed contrasting latent periods of tumour development and histological differentiation; normal keratinocyte grafts were non-tumorigenic in athymic mice. Three of four malignant cell lines formed well-differentiated tumours in syngeneic F344 rats; the tumours regressed after 10-14 days. Regressing grafts contained significantly larger numbers of NK cells (CD5-, CD8+) in the inflammatory cell infiltrate compared with that associated with primary tumours (p < 0.04). One malignant cell line and normal keratinocytes were non-tumorigenic in syngeneic hosts. The results demonstrate phenotypic variation in the cell-mediated immune responses associated with the actively growing primary SCC and the regressing tumours in syngeneic hosts and suggest that NK cells, possibly activated by local T cell responses, are important for tumour rejection in this model.
authors.affiliation: Department of Oral Medicine, Pathology & Microbiology, University of Bristol, England.
authors.forename: D W
authors.initials: DW
authors.lastname: Thomas
authors.forename: J B
authors.initials: JB
authors.lastname: Matthews
authors.forename: V
authors.initials: V
authors.lastname: Patel
authors.forename: S M
authors.initials: SM
authors.lastname: Game
authors.forename: S S
authors.initials: SS
authors.lastname: Prime
mesh_terms: D016475:3T3 Cells; D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D015703:Antigens, CD; D018956:CD5 Antigens; D016827:CD8 Antigens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D015603:Keratinocytes; D007694:Killer Cells, Natural / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000276:immunology*; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D015375:Receptors, Interleukin-2; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D018956:CD5 Antigens; D016827:CD8 Antigens; D015375:Receptors, Interleukin-2; D015112:4-Nitroquinoline-1-oxide