Macrophages and resistance to tumours. I. Inhibition of delayed-type hypersensitivity reactions by tumour cells and by soluble prducts affecting macrophages.

Mice were injected in the footpads with mixtures of an antigen (sheep red blood cells) to which they had developed delayed-type hypersensitivity (DTH) and syngeneic fibrosarcoma cells. DTH reactions were associated with depression of subsequent tumour growth compared with that in control animals. The degree of depression was proportional to the intensity of the reactions. Conversely, the presence of fibrosarcoma cells was associated with depression of the DTH reactions. Serum-free culture supernatants of all tumours tested (mouse, human and rat) depressed DTH reactions in mice, depressive activity being apparent even at dilutions greater than 1:100. Supernatants from cultures of nonmalignant cells had little or no depressive activity. Protein synthesis, but not DNA synthesis, was required for the production of the factor(s) responsible. , the active supernatants markedly inhibited macrophage migration, either spontaneously or in response to a chemotactic factor, but had much less effect on mitogen-stimulated or unstimulated lymphocyte cultures. The activity was decreased or lost after treatment with proteolytic enzymes, ribonuclease, neuraminidase or hyaluronidase. The supernatants were separated by membrane filtration into fractions of M.W. greater than, or less than 10,000. The fractions differed from each other in their effects and . Injection of concentrated supernatants from tumours together with fibrosarcoma cells led to more rapid initial tumour growth.