INFLAMMATORY CELL INFILTRATE ASSOCIATED WITH PRIMARY AND TRANSPLANTEDTUMORS IN AN INBRED MODEL OF ORAL CARCINOGENESIS

This study characterised the nature of the local cellular immune respo nses associated with an inbred animal model of oral carcinogenesis. In bred F344 rats developed moderately- to well-differentiated primary or al squamous cell carcinomas (SCC) after treatment with the carcinogen 4-nitroquinoline N-oxide (4-NQO) in vivo for 5-6 months. The inflammat ory cell infiltrate associated with the primary tumours was predominan tly of the macrophage lineage (CD45(+), Ia(+)) and contained smaller n umbers 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 p alatal SCC. By contrast to normal keratinocytes, tumour-derived cell l ines were immortal and independent of 3T3 fibroblast support. All of t he tumour-derived cell lines were tumorigenic in athymic (nu/nu) mice and showed contrasting latent periods of tumour development and histol ogical differentiation; normal keratinocyte grafts were non-tumorigeni c in athymic mice. Three of four malignant cell lines formed well-diff erentiated 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 compa red with that associated with primary tumours (p<0.04). One malignant cell line and normal keratinocytes were non-tumorigenic in syngeneic h osts. The results demonstrate phenotypic variation in the cell-mediate d immune responses associated with the actively growing primary SCC an d the regressing tumours in syngeneic hosts and suggest that NK cells, possibly activated by local T cell responses, are important for tumou r rejection in this model.