Nature 264, 356 - 359 (25 November 1976); doi:10.1038/264356a0

Non-adaptive rejection of small tumour inocula as a model of immune surveillance

A. H. GREENBERG^* & M. GREENE^†

^*Department of Pediatrics and Immunology, Manitoba Institute of Cell Biology, 700 Bannatyne Avenue, Winnipeg, Canada R3E 0V9
^†Department of Immunology, University of Manitoba, Winnipeg, Canada

THOMAS'S thesis¹ that it is a "universal requirement of multicellular organisms to preserve uniformity of cell type", led him to suggest that the phenomenon of homograft rejection represented the primary mechanism for natural defence against neoplasia. Burnet² viewed this surveillance of lethal oncogenic mutations as a function of the thymus-dependent adaptive immune system. Prehn^3,4 and others⁵⁻⁷ have criticised the Burnet model of immune surveillance because it is unable to account for several important observations: (1) the adaptive immune system, with only rare exceptions, is unable to eliminate incipient or induced tumours rather than functioning as a surveillance mechanism^4,6−8; (2) the immune response to tumours is as likely to result in immunosuppression and enhancement of tumour growth as the destruction of those tumours^6,8,9; and (3) the incidence of spontaneous tumours in athymic mice is insignificant⁵. To explain these data one must either assume that surveillance does not exist, or one must postulate that surveillance exists in a form other than the thymus-dependent adaptive immune response. We have attempted to examine the hypothesis that surveillance exists and is a non-thymus-dependent phenomenon by an experimental model in which the fate of a small tumour inoculum, simulating an oncogenic mutation, is examined after manipulation of the host's immune response.

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