So far the clearest evidence of a link between cancer and inflammation is the data demonstrating that inflammation encourages the conversion of precancerous tissue to full malignancy for many cancers. But the biological response may also be involved in initiating the disease and in advancing metastasis. Infections with Helicobacter pylori bacteria induce inflammation that greatly increases the risk of gastric cancer, and the hepatitis C virus can bring on liver cancer, to name just two cancers. Pathogens may also generate free radicals, which can damage DNA. But although inflammation may be involved from the outset, few studies have shown yet that an inflammatory condition actually alters DNA to provide the initiating spark.
The case for a role in metastasis is stronger—and recent studies lend credence to this hypothesis. Karin’s group reported in the April 5 Nature that inflammation, not genetic changes in cancer cells, spurs metastasis in mice engineered to acquire prostate cancer. The research suggests that a cytokine produced by inflammatory cells near a prostate tumor induces tumor cells to decrease production of a protein that blocks metastasis. This result, Karin notes, may explain the puzzling observation that cutting into tumors, such as for a prostate biopsy, sometimes seems to encourage metastasis. If he is correct, the inflammation generated by the intervention could be at fault. Around the same time, Pollard’s group reported in Cancer Research on a study in mice that observed that macrophages accompany breast tumor cells in their migration toward blood vessels that will transport them to remote sites, all the while sending chemical messages to their partners.
The innate immune system has received the most attention in explorations of how inflammation might cause cancer. As with innate immunity, the adaptive immune system—the T cells and antibodies produced by B cells that target specific molecules on invading cells—contributes to pathology or may also fight against it. For decades, immunotherapies designed to enhance T cell responses against cancer have been explored, though often with disappointing results.
Furthermore, an emerging picture has begun to reveal an intricate cross talk between innate and adaptive immune cells that may participate in the promoting of malignant disease. Researchers working on cancer vaccines may need to take account of these interactions in designing their treatments if they are ever to prove effective. One study showed that ovarian tumors produce a signaling molecule that serves to attract regulatory T cells, a subclass of adaptive immune cells responsible for quieting other T cells [see “Subduing Suppressors,” by Lisa Melton; Scientific American, December 2002].
Meanwhile Coussens and her colleagues at U.C.S.F. found in a 2005 study published in Cancer Cell that the removal of antibody-making B cells from mice engineered to be prone to skin cancer prevented the tissue changes and angiogenesis that are prerequisites for disease progression. In their normal role as pathogen fighters, B cell–produced antibodies circulate through the bloodstream and mark viruses and bacteria for destruction by innate immune cells. In response to a signal from precancerous tissue, however, the antibodies induce the innate system to collaborate in cancer development. An open research question is how this process starts. One possibility suggests that a cancer cell may send a message to innate immune cells, perhaps dendritic cells, that then activate B cells. Signaling may involve toll-like receptors, which have emerged as prominent intermediaries in innate immune messaging [see “Immunity’s Early Warning System,” by Luke A. J. O’Neill; Scientific American, January 2005].