GALDIERO is CO-FIRST AUTHOR. Phagocytes as Corrupted Policemen in Cancer-Related Inflammation

Inflammation is a key component of the tumor microenvironment. Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) are prototypic inflammatory cells in cancer-related inflammation. Macrophages provide a first line of resistance against infectious agents but in the ecological niche of cancer behave as corrupted policemen. TAMs promote tumor growth and metastasis by direct interactions with cancer cells, including cancer stem cells, as well as by promoting angiogenesis and tissue remodeling and suppressing effective adaptive immunity. In addition, the efficacy of chemotherapy, radiotherapy, and checkpoint blockade inhibitors is profoundly affected by regulation of TAMs. In particular, TAMs can protect and rescue tumor cells from cytotoxic therapy by orchestrating a misguided tissue repair response. Following extensive preclinical studies, there is now proof of concept that targeting tumor-promoting macrophages by diverse strategies (e.g., Trabectedin, anti-colony-stimulating factor-1 receptor antibodies) can result in antitumor activity in human cancer and further studies are ongoing. Neutrophils have long been overlooked as a minor component of the tumor microenvironment, but there is evidence for an important role of TANs in tumor progression. Targeting phagocytes (TAMs and TANs) as corrupted policemen in cancer may pave the way to innovative therapeutic strategies complementing cytoreductive therapies and immunotherapy.