Chemotherapy of malignant tumors — A self-defeating form of immunotherapy?

Abstract

Chemotherapy of malignant diseases was introduced into clinical practice during the 1940's. The initial response rate to this type of therapy is high in patients with a variety of cancers but the survival rate is affected in only a few patients, mainly in women with choriocarcinoma. Despite intensive research, the percentage of survivors following chemotherapy, for example in patients with small-cell bronchogenic cancer, has remained almost constant during the last 2 decades. The objective of the present paper is to consider the likelihood of immune mechanisms being active both in the regression and again in the later progression of tumor growth observed during treatment with cytotoxic drugs. Such a dual role for immunity appears to be possible. In contrast to most malignant cells in solid tumors, the leucocytes and leukemia cells are highly sensitive to anti-cancer agents. Thereby the drugs become immunosuppressive at a level in serum lower than that required for a direct interference with the proliferative capacity of the cells in a solid tumor. Furthermore, the cytotoxic drugs selectively influence the immune system. In the first phase of treatment the drugs enhance the effect of T-killer cells relatively by reducing blocking activity in serum; the net result being a regression in the tumor volume. However, continued chemotherapy is inconvenient for cancer patients. The treatment with cytotoxic drugs facilitates induction of immunological tolerance which promotes the acceptance of growing tumors, either from remaining tumor cells or of de novo malignancies, the immunogenicity of tumor cells and the clinical response to chemotherapy are positively related, hence supporting the theory that host tumor resistance contributes to the success of cytotoxic drugs as anti-cancer agents.