Inflammation and cancer: a double-edged sword

Abstract

Recent literature has highlighted an important role of inflammation in promoting cancer. However, the immune system can also play a central role in protecting the body against cancer as well as infection, although its role in cancer is not well understood. A study published in the September issue of Nature Medicine adds a new twist to the role of inflammation in cancer. Apetoh et al. describe how activation of innate immunity after conventional radiation or chemotherapy can trigger protective antitumor immunity.

Figure 1. HMGB1: An Endogenous Adjuvant for Antitumor Immune Responses

Damage of cancer cells (radiation, chemotherapy) leads to the release of signal molecules, e.g., HMGB1, but also other chemokines and cytokines from the necrotic and apoptotic cells. HMGB1 act as a chemoatractant for monocytes, T cells, and dendritic cells to the tumor microenvironment. Additionally, HMGB1 can bind to its main receptor RAGE, receptor for advanced glycation end products, but also interacts with TLR4 signaling. Activation of TLR4 by HMGB1 on dendritic cells induces crosspresentation and the generation of antigen-specific T cells. Activated DC or macrophages may also release tumor-promoting proinflammatory cytokines upon TLR4:HMGB1 activation.