The Suppression and Promotion of Cancer: The Dichotomy of Tumor Immunology

Abstract

A disruption in tissue homeostasis requires repair mechanisms that commence with acute inflammation. While this type of response is beneficial to the host tissue in short duration, as is the case with wound healing, numerous lines of evidence support a link between chronic inflammation and a predisposition for cancer development. In fact, neoplastic cells have been shown to arise in tissues that endure prolonged infection, irritation, or inflammation. Inflammatory molecules have also been implicated in conferring the oncogenic changes that both initiate and promote carcinogenesis. Moreover, as a tumor develops, the normal architecture of the primary tissue becomes disordered and further provokes an inflammatory response. The immune cells that infiltrate the tissue protect the body from cancer while simultaneously shaping the immunogenicity of tumor cells in an extensive and dynamic crosstalk between normal, primary tissue and cancer cells. Remarkably, tumor cells also possess the ability to promote an inflammatory response for survival. The role of inflammation in the tumor microenvironment is discussed.

ABBREVIATIONS: BCL-X_L - B-cell lymphoma-extra large, CCL22 – chemokine (C–C motif) ligand 22, CTL – cytotoxic T lymphocytes, ECM – extracellular matrix, EMT – epithelial mesenchymal transition, DAMPs - danger associated molecular patterns, HMGB1 – high mobility group B1, IFN – interferon, IL – interleukin, MALT - mucosa-associated lymphoid tissue, MDSCs - Myeloid derived suppressor cells, MYC - myelocytomatosis viral oncogene, NF-kB - nuclear factor-kB, NK – natural killer, NSAIDS – nonsteroidal anti-inflammatory drugs, RNS – reactive nitrogen species, ROS – reactive oxygen species, STAT3 – signal transducer and activator of transcription 3, TGF – transforming growth factor, Tregs – regulatory T cells, TNF- α – tumor necrosis factor α, WBCs – white blood cells, VEGF – vascular endothelial growth factor.