Accessory cell activity of tumour-associated macrophages

Abstract

On the basis of Fc receptor expression and phagocytic activity, approximately 20 -25% of the cells present within the highly immunogenic, methylcholanthrene- induced, murine fibrosarcoma FSA -R could be classified as macrophages. These cells did not express the Mac -1 antigen and were approximately 50% I -Ak- positive. The expression of I -Ak required the presence of mature T cells, and macrophages obtained from tumours grown in nu /nu hosts were I -Ak negative. Both the percentage of macrophages present within the tumour and I -Ak expression by these cells remained constant during the observed period of tumour growth and during serial passage of the tumour in vivo.

Macrophages were enriched from enzymatically disaggregated tumour cell suspensions by virtue of their capacity to adhere tightly to glass or plastic surfaces and the accessory cell activity of the adherent cell population was investigated in various well defined in vitro assay systems. Thus tumour - associated macrophages were shown to be fully capable of reconstituting the primary anti -CRBC PFC response of Sephadex G -10 passed normal spleen cells. This function required the presence of I -Ak- positive cells, and tumour- associated macro- phages treated with anti -Ia serum plus complement or obtained from tumours grown in nu /nu hosts, were inactive. Tumour - associated macrophages were also able to supply the essential cell activity required for effective cooperation between antigen- primed TH cells and normal B cells in the generation of PFC responses in vitro. Finally, tumour -associated macrophages were found to secrete a soluble factor(s) which considerably enhanced the primary anti -CRBC PFC response of whole normal spleen cells. Cell separation studies indicated that this activity was primarily a function of large macrophages. Furthermore, since macrophages treated with anti -Ia serum plus complement', or obtained from tumours grown in nu /nu hosts were as efficient as normal tumour -associated macrophages at enhancing the response, it would seem that I -Ak- positive cells were not involved in this function.

The possible significance of tumour -associated macrophage accessory cell activity is discussed.