[Possible clinical application of immunochemotherapy experimented in animals]

The author has been investigating the value of combination chemotherapy in order to augment the effects of immunotherapy (biotherapy) for experimental tumors in animals. The accumulated evidence from experimental immunochemotherapy is briefly reviewed in this paper; for example, low-dose chemotherapy not only reduced tumor burden but also brought about immunological effects such as restoration of anti-tumor immune responses. The paper also contains a summary of the immune escape mechanisms frequently observed in tumor-bearing hosts. Clinically, immunotherapy is generally applied to cancer patients in order to overcome the immune escape mechanisms and restore the immune responses to tumor cells. It is hard to expect, however, that the various strategies of cancer immunotherapy which show strong immunological effects in immunocompetent hosts would overcome the immune escape mechanisms in tumor-bearing hosts. The combined use of chemotherapy enhanced the effects of immunotherapy in the experiments. The author suggests that low-dose chemotherapy can augment the immune responses to tumor cells by overcoming the immune escape mechanisms in tumor-bearing hosts. Other findings presented are that the activity of immunosuppressor T cells or the production of an immuno-suppressive cytokine, TGF-beta, by tumor cells could be selectively inhibited by low-dose chemotherapy. On the basis of such evidence in animal experiments, the author presents his proposals for clinical cancer treatments.