Natural resistance to tumors is a heterogeneous immunological phenomenon. Evidence for non-NK cell mechanisms.

The contribution of natural killer (NK) cells to natural antitumor resistance (NR) in syngeneic DBA/2 mice was examined. Subclones from two NK-resistant tumors, P815 and L5178Y, were selected for tumorigenicity in NR assays measuring the tumor frequency of threshold doses and the elimination of 131IUdR-labelled cells. In vivo variation in sensitivity to NR did not correlate with in vitro NK cytolysis for these clones, but did for a third pair of clones from the SL2 lymphoma selected on the basis of sensitivity or resistance to NK lysis. In another series of experiments it was found that a decrease in NK cytolysis of the (NK-sensitive) SL2-5 lymphoma in aged DBA/2 contrasted with an increased rate of elimination and lower tumor frequency, suggesting that the ontogeny of these phenomena was not related. In addition, while interferon treatment of the (NK-sensitive) SL2-5 produced a corresponding decrease in susceptibility to NK cytolysis in vitro and a reduction in the in vivo elimination of 131I-labelled cells, tumor of the NK-resistant phenotype, interferon-treated in the same way, remained NK-resistant and was more rapidly eliminated. The failure to observe correlative changes in NK cytolysis associated with heterogeneity in tumorigenicity and with age-related or interferon-induced changes in NR suggest that NR cannot be due solely to an NK effector mechanism.