International scientists unlock melanoma mystery
An international network of scientists and clinicians has pieced together the puzzle of how the immune system recognises and responds to tumours like melanoma. Their work will support future research efforts for manipulating components of the immune system for safe and effective therapeutic strategies. The research findings have been published in the Journal of Clinical Investigation. Scientists from the Babraham Institute in the UK and the University of Catanzaro 'Magna Graecia' in Italy headed the research that reveals how immune cells can be harnessed to target melanoma. The study focused on human metastatic melanomas and spontaneous mouse melanomas. The results could benefit patients with metastatic melanoma, which is spread to other parts of the body via the bloodstream or lymphatic system. This latest study provides a window into the molecular interactions behind tumour growth control and how Nature Killer (NK) cells control metastatic progression in melanomas. Blood, lymph glands and tissues contain NK cells; these cells contribute to defending people against cancer, infection and transplantation. According to the researchers, NK cells are effective in targeting tumour cells but sparing healthy cells. Data from mouse models indicate that the cells not only control tumour growth, but prevent it as well. Receptors found on their cell membrane enable NK cells to detect signs of infection and recognise abnormal cells. Natural cytotoxicity receptors (NCRs) have the ability to find molecules associated with tumours. The researchers discovered two receptors that are vital for NK cell-mediated killing of melanoma cells. The team, led by Professor Francesco Colucci from the Babraham Institute and University of Catanzaro's Professor Ennio Carbone, used cell lines from 18 melanoma patients and discovered that the lines generate proteins that bind to NCRs and the DNAX accessory molecule-1 (DNAM-1), a receptor that activates NK cells. 'Interfering with the ability of DNAM-1 and NCRs to interact with proteins on melanoma cells, by either genetic means or by antibody-blockade, reduced NK cell-mediated killing of human and mouse melanoma cells lines both in vitro and in vivo,' Professor Colucci said. 'Informed by these findings, we explored the potential of NK cells in cell therapy of melanoma in "humanised" mice, which is a standard method to understand how human cells work in ... whole organisms,' he added. 'The results strikingly showed that human NK cells were able to prevent death of the mice by killing the transplanted human melanoma cells.' Professor Colucci pointed out that the research won't stop here. 'We are now setting up the next stage of the research programme. DNAM-1 and NCRs are critical parts of the machinery governing NK cell-mediated killing of melanoma cells and indicate that NK cells could be harnessed to prevent melanoma metastasis,' he remarked. The objective is to transfer the study's findings into the clinic by proposing new NK cell-based immunotherapeutic strategies for the treatment of patients with melanoma. 'We will also continue our research to understand the fundamental mechanisms of how, when and where the immune system detects early signs of cancer.' Other participants of the study included the German Cancer Research Center, Dr Mildred Scheel Foundation for Cancer Research (Germany), the Italian Cancer Research Association, Chubu University (Japan), the Karolinska Institute (Sweden), the Medical Research Council (UK) and the Fred Hutchinson Cancer Research Center (US).