Effects of immune cells and cytokines on inflammation and immunosuppression in the tumor microenvironment.

Chronic inflammation and immune responses are two core element that characterize the tumor microenvironment. A large number of immune/inflammatory cells (including tumor associated macrophages, neutrophils and myeloid derived suppressor cells) as well as cytokines (such as IL-6, IL-10, TGF-β) are present in the tumor microenvironment, which results in both a chronic inflammatory state and immunosuppression. As a consequence tumor cell migration, invasion, metastasis and anticancer drug sensitivity are modulated. On the one hand, secreted cytokines change the function of cytotoxic T lymphocytes and antigen presenting cells, thereby inhibiting tumor specific immune responses and consequently inducing a special immunosuppressive microenvironment for tumor cells. On the other hand, tumor cells change the differentiation and function of immune/inflammatory cells in the tumor microenvironment especially via the NF-κB and STAT3 signaling pathways. This may promote proliferation of tumor cells. Here we review these double edged effects of immune/inflammatory cells and cytokines on tumor cells, and explored their interactions with inflammation, hypoxia, and immune responses in the tumor microenvironment. The tumor inflammatory or immunosuppressive reactions mediated by the high activity of NF-κB or STAT3 can occur alone or simultaneously, and there is a certain connection between them. Inhibiting the NF-κB or STAT3 signaling pathway is likely to curb the growth of tumor cells, reduce the secretion of pro-inflammatory factors, and enhance the anti-tumor immune response.