Immunomodulation by Anticancer Chemotherapy: More is Not Always Better (review)

Chemotherapeutics are the mainstay of the majority of antitumor treatment strategies. These agents are usually administered at or near maximum tolerated doses resulting in frequent dramatic toxicities that compromise the quality of life and the immune response towards microbial pathogens. A number of observations suggest that low-dose treatment with chemotherapeutics is sometimes equal or even superior to high-dose chemotherapy. The efficacy of low-dose chemotherapy can be at least partly explained by the regulation of the antitumor immune response. The immunomodulatory effects of some chemotherapeutics might be further potentiated by combinations with selected biological response modifiers such as recombinant cytokines (IL-2, TNF, IL-12). The effectiveness of such treatment combinations have already proved effective in preclinical animal models. However, the efficacy in humans is still to be demonstrated in rationally designed clinical trials.