Immune cell networking in solid tumors: focus on macrophages and neutrophils.

The tumor microenvironment is composed of tumor cells, stromal cells and leukocytes, including innate and adaptive immune cells, and represents an ecological niche that regulates tumor development and progression. In general, inflammatory cells are considered to contribute to tumor progression through various mechanisms, including the formation of an immunosuppressive microenvironment. Macrophages and neutrophils are important components of the tumor microenvironment and can act as a double-edged sword, promoting or inhibiting the development of the tumor. Targeting of the immune system is emerging as an important therapeutic strategy for cancer patients. However, the efficacy of the various immunotherapies available is still limited. Given the crucial importance of the crosstalk between macrophages and neutrophils and other immune cells in the formation of the anti-tumor immune response, targeting these interactions may represent a promising therapeutic approach against cancer. Here we will review the current knowledge of the role played by macrophages and neutrophils in cancer, focusing on their interaction with other immune cells.

Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells.

Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathologic contexts by using a rigorous genetic approach. Neutrophil-deficient mice (Csf3r-/- mice) were used in classic models of colitis and colitis-associated colorectal cancer and the role of neutrophils was assessed by histologic, cellular, and molecular analyses coupled with adoptive cell transfer. We also performed correlative analyses using human datasets. Csf3r-/- mice showed increased susceptibility to colitis and colitis-associated colorectal cancer compared with control Csf3r+/+ mice and adoptive transfer of neutrophils in Csf3r-/- mice reverted the phenotype. In colitis, Csf3r-/- mice showed increased bacterial invasion and a reduced number of healing ulcers in the colon, indicating a compromised regenerative capacity of epithelial cells. Neutrophils were essential for γδ T-cell polarization and IL22 production. In patients with ulcerative colitis, expression of CSF3R was positively correlated with IL22 and IL23 expression. Moreover, gene signatures associated with epithelial-cell development, proliferation, and antimicrobial response were enriched in CSF3Rhigh patients. Our data support a model where neutrophils mediate protection against intestinal inflammation and colitis-associated colorectal cancer by controlling the intestinal microbiota and driving the activation of an IL22-dependent tissue repair pathway.