Spontaneous regression of malignant tumors: Importance of the immune system and other factors (Review).

It has been established that malignant tumors as well as metastases, of almost all histological types, can regress spontaneously although certain histological types regress more frequently than others. Various causes thereof include apoptosis, the immune system and particular conditions of the tumor microenvironment. The action of the genome in the regression of tumors is not clear, but some data, apart from those of apoptosis, support its involvement. The hypothesis that the immune system exhibits variations in efficacy, even to a marked extent, in determining partial or total regression of tumors appears to be plausible. Such variable efficacy may be supported by blockage of growth and the proliferation of cancer cells at the level of the tumor microenvironment, the intervention of various factors such as inhibitors of metalloproteinases and angiogenesis, and the absence or scarcity of particular proteins. The consequence of such a blockage would be a relative increase in the number of natural killer cells and other elements involved in the immune system in relation to the number of circulating cancer cells in the blood. A relative increase in the number of elements of the immune system is more effective than an absolute increase, since an absolute increase is able to stimulate, as frequently occurs for feedback in biological equilibria, inhibitor receptors that reduce the efficacy of the same elements (mainly natural killer and CD8(+) T cells). Such an increase in the efficacy of the immune system can lead, at least in certain cases, to the so-called spontaneous regression of malignant tumors. Clinical practice has demonstrated that metastases are less frequent in patients with renal carcinoma undergoing hemodialysis compared with patients with renal carcinoma not on hemodialysis. This finding can be interpreted, in correlation with the blockage of cancer cells in tissues, as a consequence of a partial blockage of metastatic cancer cells at the level of the dialytic membrane, with a subsequent increase in the relative efficacy of the immune system.