Reviewing the complex roles of macrophages in immune oncology, Jennifer Guerriero delves into a variety of factors including ontogeny, tissue residency, phenotype, transcriptional activity, epigenetic diversity, and the highly dynamic adaptation within the tumor microenvironment. She addresses the inadequacy of the current toolbox and the ambiguity of markers, and criticizes oversimplification, particularly in regards to the M1-M2 paradigm. Despite the very limited clinical efficacy thus far, she encourages further exploration of strategies that minimize pro-tumor functions and maximize the antitumor potential of macrophages.

Macrophages are present in all vertebrate tissues and have emerged as multifarious cells with complex roles in development, tissue homeostasis, and disease. Macrophages are a major constituent of the tumor microenvironment, where they either promote or inhibit tumorigenesis and metastasis depending on their state. Successful preclinical strategies to target macrophages for anticancer therapy are now being evaluated in the clinic and provide proof of concept that targeting macrophages may enhance current therapies; however, clinical success has been limited. This review discusses the promise of targeting macrophages for anticancer therapy, yet highlights how much is unknown regarding their ontogeny, regulation, and tissue-specific diversity. Further work might identify subsets of macrophages within different tissues, which could reveal novel therapeutic opportunities for anticancer therapy.

Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address: Jennifer_Guerriero@dfci.harvard.edu.

Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address: Jennifer_Guerriero@dfci.harvard.edu.

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