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.