The origin and function of tumor-associated macrophages

Identifying the cellular and molecular suppressors of the immune response against tumors is a popular topic in the field of tumor immunology that will provide new targets for the cancer immunotherapy. Suppressing the suppressor is a very attractive approach to enhancing the anti-tumor immune response by reversing the immunosuppression or blocking immune escape in the late stages of cancer progression. It is well known that tumors, especially at the late stage of development, can actively drive the generation of immunosuppressive or regulatory immune cell subtypes and can also induce the massive accumulation of tumor-promoting myeloid immune cells in the tumor microenvironment. For example, myeloid-derived suppressor cells, tumor-associated macrophages (TAMs) and regulatory T cells have been found to be the major tumor-promoting immune cells in the tumor microenvironment.1 Although much work has been conducted to identify the molecular mechanisms of the generation and accumulation of these types of tumor-promoting cells locally in the tumor microenvironment and systemically in the draining lymph nodes and other organs, the precise molecular mechanisms for their mobilization, differentiation, accumulation and function remain to be further investigated. Another key question in this field surrounds the difference and functional relationship between the migrating or recruited immune cells and the tissue-resident immune cells in the tumor microenvironment.