Tumour inhibition mediated by BCG in immunosuppressed rats

Two rat sarcomas (CC5 and P7) which grow progressively on transplantation into normal syngeneic hosts failed to develop when injected in admixture with the Glaxo strain of Bacillus Calmette-Guérin (BCG). Under comparable conditions, the local development of a third neoplasm (P8) was temporarily inhibited and the number of pulmonary metastases significantly reduced. Experiments were undertaken to determine the extent to which the anti-tumor action of BCG required an immunocompetent host. Rats were immunosuppressed by sub-lethal whole-body irradiation (450 R), with or without prior thymectomy and challenged with inocula of mixed BCG and tumour cells when their capacity to respond to bacterial, tumour and unrelated antigens was maximally depressed. In non-sensitized immunosuppressed rats, the ability of BCG to limit tumour outgrowth was abrogated only in the case of sarcoma CC5. For this neoplasm, immunogenic in syngeneic hosts by conventional criteria, there was a statistically significant difference in the number of tumours in immunosuppressed rats (51%) compared with non-sensitized immunocompetent controls (6%). Presensitization to either bacterial or tumour antigens, prior to thymectomy and/or irradiation, fully restored the tumour-inhibitory capacity of BCG. By contrast, sarcoma P7 was not significantly less susceptible to BCG-induced regression in non-sensitized immunosuppressed rats than in nonsensitized normal rats; and sarcoma P8 similarly failed to reveal any significant differences in susceptibility to BCG affecting primary or secondary tumour development. It is concluded that tumours may vary widely in their sensitivity to host reactions aroused by BCG. Certain neoplasms, exemplified by sarcoma CC5, require participation of an immune reaction of delayed hypersensitivity type for optimal destruction at BCG sites, while for others (e.g. sarcoma P7) an immunoreactive component of this type is not essential. By contrast, a third category of tumour (e.g. sarcoma P8) is relatively resistant to host reactions induced by the mycobacteria. An important component of BCG-mediated tumour inhibition is not dependent on an immunologically intact host.