Tumor-associated macrophages (TAMs) play a crucial role in tumor growth, progression, and metastasis. They can produce both pro-tumor and anticancer substances, and their presence in tumors can predict outcomes such as progression, metastasis, and survival. Blocking the pro-tumor effects of TAMs is a potential strategy to fight cancer.
Tumor-associated macrophages (TAMs) are inflammatory cells found in malignant tumors that play important roles in tumor growth, progression, and metastasis. Macrophages are normally part of the body’s immune response against any aberration, including foreign bodies and tumors. Tumor-associated macrophages can 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 metastasis. They can also produce anticancer substances that lead to cell killing, or cytotoxicity, and programmed cell death, or apoptosis.
Macrophages are derived from cells called monocytes, which are produced by pluripotent stem cells in the bone marrow. When an inflammation-inducing event occurs, such as an injury or infection, monocytes are recruited to the site involved and activated to become macrophages. Macrophages normally function in antigen presentation to activate other immune cells and accelerate the removal of debris, which facilitates tissue remodeling. They also enhance or amplify the immune response and are involved in gobbling up foreign bodies or infectious agents in a process called endocytosis.
When present in tumors, these macrophages become known as tumor-associated macrophages and can inhibit or enhance tumor growth and metastasis, leading to tumor progression or regression. Tumor-associated macrophages can reduce tumor growth or induce tumor regression 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), nitric oxide, and reactive oxygen intermediates (ROI).
TAMs can also release substances called cytokines and prostanoids that promote the growth of cancer cells and negate or suppress anticancer 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 can eventually metastasize.
Tumor-associated macrophages are used to predict outcomes such as progression, metastasis, and survival due to their various activities, occurrence, and quantity in some cancer types, such as human prostate cancer, breast cancer, cancer esophageal and bladder cancer. Several breast cancer studies have shown that the pro-tumor capabilities of tumor-associated macrophages are more dominant in breast cancer because they give the tumor wound healing ability. Potential strategies to fight 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.
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