Targeting the Tumor-Associated Macrophages for ‘Normalizing’ Cancer

Macrophages are a major component of the leukocyte infiltrate of tumor microenvironment. Their involvement in tumor progression was demonstrated for many cancers, including breast cancer, gastric cancer, esophageal cancer, lung cancer, cervical and ovarian cancers, melanoma and others. As macrophages are involved in many steps of cancer development such as primary tumor growth, angiogenesis and lymphangiogenesis, invasion and metastasis, suppression of cytotoxic T cell immunity, they have acquired a lot of interest as potential therapeutic targets. Numerous studies indicate the relevance of the investigation of the paradigm of the M1/M2 macrophage populations, which play a pro-inflammatory or anti-inflammatory/tumor-promoting roles during immune reactions in various pathological conditions and progression of malignant diseases. High plasticity of macrophages provides the possibility of their functional programming. Here, we discuss modern immunotherapeutic approaches of targeting tumor-infiltrating macrophages including inhibition of the recruitment of monocytes to the tumor, activation of apoptosis in macrophages, repolarization, based on the inhibition of pro-tumor activity or stimulation of anti-tumor activity.