Tumor-associated macrophages (TAMs) are inflammatory cells found in malignant tumors that play important roles in tumor growth, progression, and metastases. Macrophages are normally part of the body’s immune response against any aberration, including foreign bodies and tumors. Tumor-associated macrophages may produce pro-tumor substances, such as those that enable both the formation of new blood vessels, or angiogenesis, and tissue remodeling, leading to tumor progression and metastases. They may also produce anti-tumor substances that lead to cell killing, or cytotoxicity, and programmed cell death, or apoptosis.
Macrophages are derived from cells called monocytes, which are produced from pluripotent stem cells in bone marrow. When there is an event that induces inflammation, such as injury or infection, monocytes are recruited to the involved site and are activated to become macrophages. Macrophages normally function in antigen presentation in order to activate other immune cells and hasten the removal of debris, which facilitates tissue remodeling. They also enhance or amplify the immune response and are involved in eating up foreign bodies or infectious agents in a process called endocytosis.
When present in tumors, these macrophages become known as tumor-associated macrophages and may either inhibit or enhance tumor growth and metastases, leading to either progression or regression of the tumor. Tumor-associated macrophages can reduce the growth or induce the regression of the tumor through cytotoxic, cell-killing, or cell lysis mechanisms. Some substances released by tumor-associated macrophages that induce cell killing include hydrogen peroxidase, interleukin-1 (IL-1), tumor necrosis factor (TNF), nitrogen oxide, and reactive oxygen intermediates (ROIs).
TAMs may also release substances called cytokines and prostanoids that promote tumor cell growth and negate or suppress anti-tumor T cells and natural killer (NK) cells. These pro-tumor substances include interleukin-10 (IL-10) and prostaglandin E2 (PGE2). Through the release of various pro-tumor substances, the malignancy grows and may eventually metastasize.
Tumor-associated macrophages are being used for predicting outcomes such as progression, metastases, and survival because of their various activities, their presence, and their amount in certain cancers, such as human prostate cancer, breast cancer, esophageal cancer, and bladder cancer. Multiple breast cancer studies have shown that the pro-tumor capabilities of tumor-associated macrophages are more dominant in breast cancer because they lend a wound-healing ability to the tumor. Potential strategies for fighting cancer now include blocking the pro-tumor effects of tumor-associated macrophages. An example of this is the development of trabectedin, a drug from a marine turbinate that exhibits cytotoxicity against TAMs.