The grafting of cancerous cells in normal humans usually leads to the appearance of a growing tumor which (315) after a period of days, almost always suffers the same fate as a moderately heterogeneous transplant: death followed by resorption or expulsion. The time when this process occurs indicates the allergic nature of the defense mechanism. It is highly probable that, without the intervention of this efficient allergic defense, the cancerous process would have continued to evolve.

Such continued growth occurs if grafts are made in subjects already having their own cancerous process. This would indicate that the allergic defense mechanism against the graft is no longer operating in these cases. The fact that a cancerous subject accepts a new tumor graft while the normal one rejects it indicates that defense processes are different for the normal and this cancerous subject. The inability of these subjects to reject a grafted tumor through an allergic response appears to be the major immunological difference between the normal and the cancerous subject. Still more important is the fact that in cancer patients, the anomaly would correspond to a loss of the capacity to reject the grafted tumor which the normal subject seems to have.

In trying to determine the nature of the immunological anomaly in the evolution of a spontaneous cancer in patients, we have to relate it to this loss of the defense processes as seen above.

In studying this occurrence in general, a loss of defense against an antigen can be conceived to occur for any of the three different mechanisms involved in defense: primary, allergic or protective. In cases when this takes place, the loss of the protective stage will take place first. The allergic defense will be affected next and finally, the primary response. This explains why the inability of an individual to achieve one stage of the defense leaves the defense resting in the immediately previous stage. The inability to manufacture protective globulinic antibodies, for instance, will leave an individual in the allergic stage which, in the development of defense, precedes manufacture of the immune antibodies. This results in a potential allergic condition if the antigen is absent or an actual allergic condition if the antigen is present. We have seen that this occurs in most of the chronic infectious conditions. Similarly, with the inability of an organism to manufacture coagulant antibodies, the defense remains in the previous defense stage, the primary lipidic one.

Before going further, we have to discuss a factor believed by many authors to be involved also in the defense mechanism against cancer. A few years ago, the defense mechanism in general had been related to the properdin system. However, when considered in terms of the systematization of the defense processes, properdin has to be regarded as a nonspecific direct anti noxious reaction. It appears to be involved in the antiheterogeneous defense response, appearing after the enzymatic hydrolytic attack and at the beginning of the prolonged lipidic intervention.

The decrease in the properdin content of the blood of subjects with cancer has caused various authors to try to explain through it the differences in the reaction of cancerous and normal subjects toward a new transplant. The analysis of the conditions under which this occurs, however, has shown us that the anomaly does not reside in the antiheterogeneous processes of defense, which are the same against antigen and allergic complex, but in the allergic reaction itself. From the immunological point of view, the difference between a normal subject and one with invasive cancer resides in the loss of capacity to induce the second type of defense, the allergic, toward the cancerous tissue. Corresponding to an inability to manufacture coagulant antibodies, this deficiency would explain the lack of respective antiheterogeneous reaction toward the antigen coagulant antibodies complex and consequently the low blood content of properdin seen in these cases.

Failure of the allergic defense mechanism specifically against cancer entities need not mean general failure of allergic defense. The failure may be limited to inability to manufacture allergic antibodies against a specific antigen. We have seen, especially for the infectious diseases, that primary and allergic processes can occur with great intensity and still not be qualitatively efficient. The agent, the microbe, for instance, can still remain present despite even violent allergic reactions. The mere presence of defense processes does not implicitly mean successful defense; they may be qualitatively insufficient.

In cancer, if the allergic defense is insufficient, two eventualities have to be considered: either the organism in general cannot pass into the allergic stage of defense and therefore is unable to manufacture allergic antibodies, or this response is only qualitatively insufficient. In the latter case, the general and even local reactions could be quite intensive but still be ineffective. This seems to occur only in certain forms of cancer such as those with a high inflammatory process; for instance, in the inflammatory form of breast carcinoma. As this cancer starts and evolves as an acute mastitis, very intensive defensive processes, apparently only of the primary stage, occur. But they are unable to check the disease which usually evolves even more rapidly in these cases. This is also true for other cancers where fever is present, indicating a prolonged primary, toxic stage. The lack of local reaction seen at the site of the growing transplant in the cancerous subject at the time when the normal individual kills or rejects the transplant points to the fact that the anomaly resides in qualitative inability to manufacture allergic antibodies.

The next problem was to investigate the reason for the failure of allergic defense against the tumors. We could show that the cancerous subject has not lost the capacity in general to manufacture coagulant antibodies. Even subjects with very widely spread cancer were able to respond with a local skin allergic reaction to a second injection of an antigen (proteins from mollusks) made more than ten days after a first preparatory one. (Note 7) Their inability to fight transplanted cancer cells through a similar allergic reaction indicates that the loss of this capacity is not general but relatively specific toward the cancerous cells. The lack of an intensive inflammatory process, as well as the existence of high amounts of lipids in the cancerous tissue, also would indicate indirectly an inability of the cancerous subject to resolve the existing immunological problem of fighting cancer through an allergic reaction. The presence of large amounts of lipids indicates that the defense mechanism has been arrested in the stage of pronounced lipidic predominance. Abnormal amounts of lipids thus could represent an indirect means of recognizing the failure of an allergic response to cancerous entities.

The next problem was to try to determine where in the organization the failure occurs. The different levels of the organization are independent to a certain degree and passage of an abnormality from one level to another induces hierarchic progression of the condition. This has posed the problem of the progressive loss at the different levels of the natural capacity to defend against cancer. Recently many investigators have shown that cancer cells pass into the lymphatic system and into the general circulation in a much higher proportion than had been suspected before. Malignant cells in the circulation are destroyed, however, by the defense means which are not lost at this level. The same patient thus may still have an actively growing cancer at the tissular level, indicating that this defense process, although successful for the higher levels of the organization, does not intervene at this lower level.

The hierarchic progression of cancer can be seen as a progressive loss of the immunological defense capacity. While the organism conserves the capacity to fight at a higher level, a lower hierarchic entity no longer opposes the cancerous condition. It is not the absence of cancerous cells in blood or organs which explains the lack of an explosive spread of the disease, but the presence of efficient defense means at these levels which keeps a cancer still localized.