Immunomodulation by cancer chemotherapeutic agents

Cytotoxic agents may specifically interfere with the different components of cellular and humoral immunity, and consequently modulate the responses in opposite directions, by not only inducing impairment but also augmenting some immune functions. They may also modulate tumor antigenic expression, leading to increased immunogenicity. Glucocorticoids at sufficiently high concentrations can inhibit virtually any function of lymphocytes, NK cells, monocytes and macrophages. Azathioprine and other antimetabolites, such as 6-mercaptopurine, methotrexate and cytarabine, have a similar generalized immunosuppressive activity and may be used therapeutically for this purpose in the clinic. Cyclophosphamide exerts an immunosuppressive or an immunostimulating effect when given at high or low doses, respectively. The marked Cy-induced inhibition of T suppressor lymphocytes, the predominant immune cell population in cancer patients favoring tumor growth, may have important therapeutic significance. DX enhances proliferation of lymphocytes in the presence of mitogens, but may inhibit antibody production; it also increases the tumoricidal activity of monocytes and macrophages and does not alter substantially NK cytolytic activity. A detailed study of drug effects on the tumor and host immune system may contribute to their more rational use in cancer chemotherapy with regard to toxicity and efficacy.