Chronic Inflammation and Cytokines in the Tumor Microenvironment
Figure 1
Schematic illustration of the role of cytokines in carcinogenesis. (a) During tissue injury or infection, an immune response activates the expression of proinflammatory mediators, such as TNF-α, IL-6, and IL-8 from macrophages and neutrophils. These cytokines can disrupt the epithelial barrier, induce RONS, and promote the infiltration of other inflammatory cells. (b) In chronic inflammation, proinflammatory cytokines such as TNF-α can induce DNA damage through RONS, which leads to tumor initiation. TGF- can promote malignant transformation through EMT activation. Cytokines derived from CD4+ lymphocytes, such as IFN-γ, IL-10, and IL-17, can participate in epithelial barrier disruption, M2 phenotypic transitions of macrophages, and angiogenesis, respectively. (c) Tumor growth and invasion are also favored by proinflammatory cytokines that stimulate cell proliferation, reduce apoptosis, and enhance EMT and angiogenesis; the latter is facilitated by VEGF and IL-8. Anti-inflammatory cytokines, such as IL-10 and TGF-, contribute to tumor immune evasion. (d) Tumor-associated macrophages (TAM), tumor-infiltrating lymphocytes (TIL), and cancer-associated fibroblasts (CAF) secrete several factors that contribute to tumor growth and metastasis, while maintaining the immunosuppressive milieu.
