On the immunostimulatory hypothesis of cancer

There is a rather generalized belief that the worst possible outcome for the application of immunological therapies against cancer is a null effect on tumor growth. However, a significant body of evidence summarized in the immunostimulatory hypothesis of cancer suggests that, upon certain circumstances, the growth of incipient and established tumors can be accelerated rather than inhibited by the immune response supposedly mounted to limit tumor growth. In order to provide more compelling evidence of this proposition, we have explored the growth behavior characteristics of twelve murine tumors -most of them of spontaneous origin- arisen in the colony of our laboratory, in putatively immunized and control mice. Using classical immunization procedures, 8 out of 12 tumors were actually stimulated in "immunized" mice while the remaining 4 were neither inhibited nor stimulated. Further, even these apparently non-antigenic tumors could reveal some antigenicity if more stringent than classical immunization procedures were used. This possibility was suggested by the results obtained with one of these four apparently non-antigenic tumors: the LB lymphoma. In effect, upon these stringent immunization pretreatments, LB was slightly inhibited or stimulated, depending on the titer of the immune reaction mounted against the tumor, with higher titers rendering inhibition and lower titers rendering tumor stimulation. All the above results are consistent with the immunostimulatory hypothesis that entails the important therapeutic implications -contrary to the orthodoxy- that, anti-tumor vaccines may run a real risk of doing harm if the vaccine-induced immunity is too weak to move the reaction into the inhibitory part of the immune response curve and that, a slight and prolonged immunodepression -rather than an immunostimulation- might interfere with the progression of some tumors and thus be an aid to cytotoxic therapies.