title: Interplay between the toxic effects of anticancer drugs and host antitumor immunity in cancer therapy.
abstract: The results accumulated thus far illustrate that the therapeutic efficacy of many anticancer drugs depends not only on the direct tumoricidal/tumoristatic activity of the drug but also on the contribution to tumor eradication of antitumor immunity which emerges after the chemotherapy. When a low dose of anticancer drug is employed, it reduces the tumor burden to a lesser extent than a high dose of drug. Consequently, in order for the low dose of drug to be as effective as a high dose of drug, antitumor immunity has to control a larger tumor burden than that controlled by the immune system following high-dose chemotherapy. This was shown to happen in several experimental tumor models wherein the low dose of drug greatly potentiated host antitumor immunity while the high dose of drug either potentiated host antitumor immunity to a lesser extent, did not potentiate it at all, or actually exerted a suppressive effect on host antitumor immunity. As a result of the immunopotentiating activity of the low dose of drug, tumor-bearing animals which did not exhibit concomitant antitumor immunity due to the inhibitory activity of suppressor cells, developed a very potent antitumor immunity shortly after the chemotherapy. The immunopotentiating effect of the low dose of drug was attributed in these situations to drug-mediated selective elimination of suppressor cell activity and possibly also to drug-mediated enhancement in the activity of T cells of the helper phenotype through elevation in IL-2 production. Antitumor immunity can also facilitate the therapeutic effectiveness of high-dose chemotherapy. Therefore, it is important to determine the conditions under which high-dose chemotherapy can also potentiate host antitumor immunity. From the rodent data available, the picture emerges that the maturity of antitumor immunity at the time of the chemotherapy is an important factor in determining if the high dose of drug leads to immunosuppression or immunopotentiation. When a high dose of drug is administered to tumor bearers with a fully developed antitumor immune response, it is more likely to lead to potentiation of host antitumor immunity than when the high dose of drug is administered to tumor bearers that have not yet achieved the full maturity of their antitumor immune response. In order to achieve the maximal enhancement of antitumor immunity in hitherto immunosuppressed tumor bearers, the suppressor-cell pool should be more sensitive to the toxic effects of the anticancer drugs than are cells involved in immune-tumor eradication.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide