Interactions among myeloid regulatory cells in cancer

Viktor Umansky, Gosse J. Adema, Jaroslaw Baran, Sven Brandau, Jo A. Van Ginderachter, Xiaoying Hu, Jadwiga Jablonska, Slavko Mojsilovic, Helen A. Papadaki, Yago Pico de Coaña, Kim C. M. Santegoets, Juan F. Santibanez, Karine Serre, Yu Si, Isabela Sieminska, Maria Velegraki, Zvi G. Fridlender

Mounting evidence has accumulated on the critical role of the different myeloid cells in the regulation of the cancerous process, and in particular in the modulation of the immune reaction to cancer. Myeloid cells are a major component of host cells infiltrating tumors, interacting with each other, with tumor cells and other stromal cells, and demonstrating a prominent plasticity. We describe here various myeloid regulatory cells (MRCs) in mice and human as well as their relevant therapeutic targets. We first address the role of the monocytes and macrophages that can contribute to angiogenesis, immunosuppression and metastatic dissemination. Next, we discuss the differential role of neutrophil subsets in tumor development, enhancing the dual and sometimes contradicting role of these cells. A heterogeneous population of immature myeloid cells, MDSCs, was shown to be generated and accumulated during tumor progression as well as to be an important player in cancer-related immune suppression. Lastly, we discuss the role of myeloid DCs, which can either contribute to effective anti-tumor responses or play a more regulatory role. We believe that MRCs play a critical role in cancer-related immune regulation and suggest that future anti-cancer therapies will focus on these abundant cells.