Fighting disease with disease.

Small size inocula (101-103 cells) of cells from a syngeneic methylcholanthrene-induced fibro-sarcoma (FSA) induced tolerance when injected s.c. into C3Hf mice. Mice were unable to respond to subsequent challenge with moderate, immunogenic doses of FSA. Tolerance was demonstrated in an in vivo transfer (Winn) assay and an in vitro tumour-specific TH cell assay. Low zone tolerance was associated with the presence of tumour-specific Ts cells in the spleen. Moderate size inocula (104-106 FSA cells) were immunogenic but larger cell doses (>106) were again tolerogenic. In the high zone, tolerance was associated with both tumour-specific Ts cells and non T suppressor cells that were not tumour-specific. These results support the view that immunogenic tumours, as they grow from small cell numbers, might be able to escape host surveillance by specifically tolerizing the immune system. They also suggest that large tumour burdens can interfere with the host's immune response by inducing suppressor cells. An important concept in tumour immunology is that tumours grow only if they can avoid host immune responses. An extension of this concept is that immune responses are selective forces during tumour progression. Numerous mechanisms have been envisaged and investigated by which tumours could escape immune defences. Early research revolved around lack of immunogenicity of tumours, shedding and modulation of cell surface antigens and blocking of tumour reactive lymphocytes by antigen-antibody complexes (Hellstrom & Hellstrom, 1969). More recent studies take into account our knowledge that the immune system is composed of complex interacting and self-regulating networks of cells and soluble factors and have focused on whether antigens on progressor tumours have properties that allow them to avoid protective immunity, for example by preferentially stimulating suppressor cell circuits (Moser et al. The ability of many tumours to stimulate Ts has been established although the conditions under which they are generated and the extent to which they facilitate growth of primary tumours still requires clarification. In our previous studies with a transplantable murine fibrosarcoma (FSA) we found both tumour-specific Ts and non-tumour-specific non-T suppressor cells in the spleens of tumour-bearing mice in the later stages of tumour growth (Howie & McBride, 1982; McBride & Howie, 1984). The tumour grew initially in the face of developing systemic responses that were demon-strably protective. Concomitant immunity (Milas et al., 1982) and tumour-specific responses could be demonstrated by both in vitro (Howie & McBride, 1982; McBride & Howie, 1984) and in vivo (Peters et al., …