Immune modulation by agents used in the prevention and treatment of colon and pancreatic cancers

Many effects of anticancer drugs have been investigated over the past 50 years; however, the mechanisms that control immuno modulatory effects of these drugs are not well understood. Macrophages, regulatory T cells, dendritic cells, and pro-inflammatory cytokines modify the colon and pancreatic tumor microenvironments and contribute to tolerance to tumor-associated antigens and immune escape. The initiation and aggressive progression of disease in colon and pancreatic cancers is a consequence of this immune escape and tolerance. Contrasting with immune tolerance are antitumor effects, which include natural killer cell-mediated production of cytotoxic effectors that kill tumor cells. It is therefore incumbent upon researchers to understand the mechanisms regulating tolerance and rejection of colon and pancreatic cancers and to devise immune prevention and immune therapies that stimulate tumor rejection rather than tolerance. This chapter will provide an overview of the immune modulatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs), statins, selective estrogen response modulators (SERMs), rexinoids, antidiabetic drugs, and natural agents (triterpenoids, phytochemicals, fatty acids) that have documented effects on colon and pancreatic cancers. Prevention of colorectal cancer and pancreatic cancer may be enhanced by strategies for selection and development of agents to improve NK cell cytotoxicity or immune surveillance.