Although the host immune system is known to have conflicting roles in cancer initiation and progression, both acting as a surveillance and elimination system but also assisting expansion and metastatic spread of tumours, very little is known about the very early role of the immune system in cancer. Using zebrafish larvae, researchers at the University of Bristol, the University of Manchester and the FIRC Institute of Molecular Oncology in Milan have now been able to observe, for the first time, how oncogene-transformed cells in the skin co-opt the innate immune system to promote their growth from the very earliest stages of development. The team exploited the translucency of the larvae to obtain live images of the earliest interactions between the cancer cells and the immune environment. Using larvae with fluorescently tagged leukocytes, the team were able to observe recruitment of neutrophils and macrophages to oncogene-transformed melanocytes or mucus-secreting cells. As well as engulfment of the transformed cells, the team saw many examples of cytoplasmic tethers linking the two cell types.
They discovered that a key attractant for the leukocytes was hydrogen peroxide. Both the transformed cells themselves and otherwise healthy neighbouring cells were found to produce hydrogen peroxide, which is also a key molecule that recruits neutrophils to a wound. Blocking the synthesis of hydrogen peroxide prevented recruitment of immune cells and reduced the number of transformed cells, suggesting that immune cells may provide trophic support to the transformed cells just as they promote repair at a site of tissue injury. Unlike the case of wound healing, however, where the inflammatory response resolves, the inflammatory response to transformed cells seems to amplify and progress towards a chronic inflammatory state similar to that seen in chronic non-healing wounds.