Immune-promoted tumor cell invasion and metastasis. New considerations in cancer therapy.

Abstract

Available information shows that the immune system does not spontaneously reject malignant tumors. In addition, medical maneuvers to stimulate an immune response against established tumors do not show repetitive good results. Apparently, malignant tumor cells escape immune recognition and attack through multiple molecular mechanisms. Laboratory experiments show that properly stimulated specific CD8+ T cells, some CD4+ T cells, NK cells, and macrophages are capable of killing tumor cells. But, even in experimentally controlled conditions, a regular, complete, reliable and applicable tumor immune rejection has not been achieved yet. The birth of monoclonal antibodies, easy to produce in the laboratory and with very restricted target recognition, initiated a wave of expectation in the anti-cancer immune therapy believers. The “magic bullet” concept became popular, many new tumor antigens were discovered and new anti-tumor antigen antibodies developed. Thirty years after monoclonal antibodies introduction, few if any of those antibodies have shown a reliable anticancer curative effect. A question is raised looking at this defeating scenario: Is the immune system prepared to reject tumors? The plain answer to this question is another question: Why not? The immune system recognizes damaged cells and eliminates them in a continuous process of tissue repair. If tumor cells are identified as damaged cells the immune system should eliminate them. Nevertheless, in normally differentiated tissues, after elimination of damaged cells, a process of cell substitution and remodeling takes place based on recruitment of reserve cells and stem cells. Normal tissue repair involves, among other features, immune system cells and blood cells. Bone marrow derived scavenger cells remove cell debris. A controlled inflammatory cellular infiltration guaranties local replacement of connective matrix, cell motility/translocation, and neoangiogenesis. Apparently, tumor tissue replacement doesn’t need stem cells while tumor cells can divide infinitely. Therefore, the elimination of tumor cells is a mater of imbalance: if the elimination process is faster the tumor disappear, but if the replacement process is faster the tumor grows. In addition, the particular performance of tumor cells disturbs the repair process and, in consequence, tumor connective matrix replacement, cell relocation, and neoangiogenesis are in chaos.