Inflammatory Mediators Hold the Key to Dendritic Cell Suppression and Tumor Progression

K.      C. Sheng; M.      D. Wright; V.      Apostolopoulos

doi:10.2174/092986711798347207

Abstract

Cancer has long been considered a disease that is associated with immune tolerance. Its connection with inflammation initially appears paradoxical. During the last decade, it has become increasingly clear that immune infiltrates form an integral part of tumor and critically contribute to its development and progression. In the tumor milieu, a variety of inflammatory mediators, such as cytokines (IL- 6, IL-10, VEGF, TGFβ, M-CSF and GM-CSF), chemokines (CCL20 and CXCL8), hormones (prostanoids like PGE2), reactive oxygen species and cellular constituents (gangliosides), are continuously produced. These mediators represent a critical interface between immune and neoplastic compartments. Not only do they continuously support tumor survival and expansion, but suppress the function of immune cells, notably, dendritic cells - the powerful antigen presenting cells that are crucial for induction of tumor-specific immune responses. This review summarizes such a dual role of inflammatory factors and discusses the controversies associated with specific mediators including IL-10, GM-CSF and ROS in tumor and immune modulation. Identifying the inflammatory signature of cancer patients hence represents a critical task for individualized immunotherapy in the future.

Keywords: Inflammation, inflammatory mediators, tumor, cancer, dendritic cells, immune tolerance, tumor milieu, pathogenic threat, immunotherapeutics, neoplastic compartments