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The origin and function of tumor-associated macrophages

Cellular & Molecular Immunology volume 12, pages 1–4 (2015)Cite this article

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.

As an important type of immune cells in the tumor microenvironment, macrophages have been demonstrated to be important in tumor progression, depending on the stage of tumor development and the tumor type.7 Generally, TAMs are accepted to promote tumor progression via different mechanisms. Macrophages are a heterogeneous cell population that can be conventionally divided into two subgroups: M1 and M2. M1-type macrophages, which are classically activated, play important roles in the innate response against invading pathogens. M2-type macrophages, which are alternatively activated, play important roles in tissue repair and tumor progression. Previous studies have shown that Notch signaling plays a decisive role in the polarization of M2 macrophages.8,9 A recent study shows that mouse peritoneal macrophages can specifically express the transcription factor Gata6, which can affect the phenotype of macrophages by altering their transcriptome, thus contributing to the inflammatory response and the renewal of macrophages in the inflammatory response.10 Furthermore, the localization of tissue-specific macrophages and the polarization of macrophage function can be determined, at least partially, by this pathway.11 Several cytokines, such as IL-6, have been found to be important in the development and maintenance of the macrophage subsets and their functions in inflammation and tissue homeostasis.12 Much work has been performed to identify the soluble factors, such as chemokines and growth factors, in polarizing macrophage function in tumor progression. For example, the chemokine CCL2 and macrophage colony-stimulating factor can recruit monocytes to the tumor tissue, and then IL-4, IL-10, IL-13 and other cytokines in the tumor microenvironment can induce the monocytes to differentiate into TAMs.13 TAMs have a very weak ability to present antigens but exhibit a very potent ability to promote tumor progression through a variety of mechanisms. However, the detailed mechanisms for the recruitment and tumor-promoting function of TAMs are not fully understood; thus, further investigation is required to identify new targets for cancer immunotherapy.

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  1. National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China

    Yang Liu & Xuetao Cao

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Liu, Y., Cao, X. The origin and function of tumor-associated macrophages. Cell Mol Immunol 12, 1–4 (2015). https://doi.org/10.1038/cmi.2014.83

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