We used the data obtained from the analysis of the defense process against cells and tissues in the study of the immunological problem of cancer. The different cancerous hierarchic entities, as defined previously may be considered to correspond, up to a certain point, to heterogeneous entities—the grafted tumors to transplants and the spontaneous tumors to heterogenized entities of the individual.

We tried, in a first series of experiments, to follow the intervention of the different mechanisms of defense on grafted tumors in animals, employing transplants of various degrees of heterogeneity. Different types of tumors were used. Highly heterogeneous tumors obtained from species other than the host would not grow when transplanted. The death of the transplant, even its rejection if mechanically possible, occurs in a short time. The necrosis of the transplant and the relatively wide inflammatory process that develops around it immediately after the graft indicate the intervention of the first stage of the defense reaction from the cellular to the organic level.

With a second group of tumors, usually from the same species or even moderately heterogeneous, the grafts take and the tumors grow for a time. Often, around the 8th to the 15th day, the transplant starts to show profound changes. The changes affect the entire tumor which involutes rapidly and is often expelled. That this is due to allergic reaction could be shown by the following experiment. Fragments of the same kind of tumor which had been obtained from different animals were transplanted at 2 to 3 day intervals in the same host. In spite of the different ages of the transplants, the death and rejection of all occurred at short intervals and in the same manner, indicating the intervention of a mechanism taking place in the host and relatively independent of the evolution of the transplant itself. Such a mechanism would be the intervention of allergic antibodies.

In a third group of grafts of low heterogeneity, the tumors continue to evolve for an even longer period of time, and it is only in a few animals that these tumors are entirely rejected. This change, which consists of cytolysis of the tumor, takes a certain time to be completed, which indicates that it probably results from the intervention of protective antibodies. The first and the second defense mechanisms appeared to be inadequate to conquer the tumor and it was the third stage, with formation of protective antibodies, which apparently was able to accomplish it. This mechanism is confirmed by the fact that later grafts are negative from the time they are transplanted, through cytolytic changes in the tumor and not through an intensive inflammatory process as seen in the primary reaction. The immunological nature of the defense in these cases could be seen also through the passive immunity which could be induced in other animals with the serum of the host.