Appropriate and rational modulation of innate immunity may enhance the therapeutic efficacy of emerging immune therapies for treating cancer. One of the crucial cells of innate immunity is the macrophage. The purpose of this article was to review those issues that suggest ways of exploiting macrophage local functions in immune therapy, and to discuss the suitability of low molecular-weight lipopolysaccharides as potent modulators of macrophage functions for immune therapy of cancer.