The effect of cell dose and distribution on the development of a transplanted tumour

Abstract

Experiments with an isogeneically-transplanted murine sarcoma which has a TD 50 of about 30 cells have shown inter alia that for a given total cell dose the proportion of mice which develop tumours is not altered by distributing the dose among 10 sites as against concentrating it in a single site, whereas the tumour volume per mouse 24 days after inoculation may be markedly reduced. At doses of 100 cells per site or more the chance of take at a site is not influenced by the presence of other sites, but the mean rate of growth at a site is reduced in the presence of other sites. In T-cell deprived mice single site inoculation of 1000 cells results in slower growth than in intact mice, but distribution of the dose among multiple sites in deprived mice does does not further reduce the total tumour volume (measured 18 or 24 days after inoculation). In the light of these and other findings it is postulated that, following tumour inoculation, there is an early local host reaction probably mediated by macrophages, which causes rapid destruction of some of the transplanted cells, the number destroyed depending partly on the intensity of the reaction and partly on a mutually protective effect of the tumour cells. With tumours which possess tumour-specific transplantation antigens there is in addition a slower immunological reaction which may destroy some or all of the cells which have survived the early reaction. A modification of the hypothesis put foreward previously to account for the slower growth of the tumour in T-cell deficient mice is proposed.