- Email: [email protected]
Mouse fights cancer with innate immunity
Newsdesk
Researchers at the Wake Forest University School of Medicine, NC, USA, have uncovered a new mechanism by which the immune system can recognise and destroy tumours. Zheng Cui and his colleagues have established a colony of mice in which resistance to implanted tumours is dominantly inherited. The resistance mechanism, they report, involves cells of the innate immune system. The idea that the immune system might help to protect animals and people from cancer was first suggested nearly 100 years ago by Paul Ehrlich. In the 1960s, Macfarlane Burnet and Lewis Thomas developed the idea into the cancer immunosurveillance hypothesis. Because genetic changes, some of which would represent a step towards malignancy, must be common in somatic cells, they proposed that an immunological mechanism might eliminate mutant cells. The hypothesis fell out of favour when no strong supportive evidence was found, but more recent data have led to a resurgence of interest (Nat Immunol 2002; 3: 991–98). Cui became interested in immunosurveillance when in April 1999 he noticed that a mouse he had injected with an aggressive sarcoma did not develop a tumour as expected. “I was trying to grow ascites from which to purify an antibody”, he explains, “so when the first injection failed to take, I tried again”. Again, no tumour grew. The mouse was eventually given five injections without succumbing to cancer. “I had never seen anything like this”, says Cui. “I was injecting an MHC-negative tumour that normally grows in all mice.” Despite some initial scepticism from colleagues, Cui decided to see if this tumour resistance could be passed on to the offspring of his original failed experiment. To his surprise, the resistance segregated as a dominant trait and Cui now has a colony of 700 mice that carries the trait, which provides resistance to all tumour cell lines so far tested (Proc Natl Acad Sci USA, published online April 30; doi:10.1073/pnas.1031601100). “The clincher for me”, continues Cui, “came when we videotaped leukocytes from
328
Courtesy of Z Cui
Mouse fights cancer with innate immunity
Scanning electron micrograph of an immune cell attacking a cancer cell.
resistant animals attacking tumour cells in vitro”. The tumour cells just popped open, he says, while the normal cells remained unscathed (www.wfubmc. edu/pathology/research/srmouse.htm). The researchers are now trying to
identify which immune cells are responsible for tumour-cell killing and how they recognise the malignant cells. “This is highly original, unexpected and potentially exciting work”, comments Mark Smyth (Peter MacCallum Cancer Institute, Melbourne, Australia). He adds that it is now critical to identify the gene that provides resistance and to see whether spontaneous tumours can develop in the resistant mice. By determining exactly how the innate immune system recognises cancers, it may be possible to develop a new immunological strategy for the treatment of advanced tumours, conclude Smyth and Cui. Jane Bradbury
New boost for Italian cancer research Italy spends 1·1% of their GDP on research compared with around 2% in France, Germany and Britain. “Government financing for biological and biomedical research is laughable”, comments Pier Paolo Di Fiore, director of the Institute for Molecular Medicine (IFOM). “Basically we all live off grants given by a few major charities.” But, the opening of a new cancer research centre in Milan in early April, may prove to be the stimulus Italian research has been waiting for. The IFOM was created by Italy’s largest biomedical research charity the Foundation for Cancer Research (FIRC). The centre will employ around 300 researchers and concentrate on nanotechnology, bioinformatics, and structural biology. FIRC will provide equipment and salaries for infrastructure and common services in Italy, whereas research institutes including the European Institute of Oncology, and Mario Negri Pharmacological Research Institute will provide personnel. The facilities will subsequently be opened to other oncology centres across Italy. “Instead of one or two groups in federal institutions, we will end up with 20 groups working in similar fields who all have access to state-of-
the-art equipment and know-how for post-genomic research”, says Di Fiore. Another problem that has plagued Italian cancer research is fragmentation, a phenomenon Di Fiore attributes to the lack of a central grant awarding agency. “Varying initiatives start from the Health Ministry, Research Ministry, National Research Council, Industry Ministry, etc. So it is very difficult to know how much money is given and what the criteria are...most financing still follows semi-obscure reviewing processes.” He argues that concentrating research facilities is an attempt to compensate for these handicaps and prevent young researchers leaving for other countries. “We need to focus science in a few very good centres”, comments Marco Presta, Brescia University, Italy. However, he fears that these investments will exacerbate the funding shortage in university laboratories: “The risk is that in 10 years time a few excellent places will be islands in a sea of mediocrity.” Di Fiore concurs: “You cannot just build research by financing excellence, you’ve got to finance the whole network, including the small labs that do the training. That can only happen with government money.” Claudia Orellana
THE LANCET Oncology Vol 4 June 2003
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Researchers at the Wake Forest University School of Medicine, NC, USA, have uncovered a new mechanism by which the immune system can recognise and destroy tumours. Zheng Cui and his colleagues have established a colony of mice in which resistance to implanted tumours is dominantly inherited. The resistance mechanism, they report, involves cells of the innate immune system. The idea that the immune system might help to protect animals and people from cancer was first suggested nearly 100 years ago by Paul Ehrlich. In the 1960s, Macfarlane Burnet and Lewis Thomas developed the idea into the cancer immunosurveillance hypothesis. Because genetic changes, some of which would represent a step towards malignancy, must be common in somatic cells, they proposed that an immunological mechanism might eliminate mutant cells. The hypothesis fell out of favour when no strong supportive evidence was found, but more recent data have led to a resurgence of interest (Nat Immunol 2002; 3: 991–98). Cui became interested in immunosurveillance when in April 1999 he noticed that a mouse he had injected with an aggressive sarcoma did not develop a tumour as expected. “I was trying to grow ascites from which to purify an antibody”, he explains, “so when the first injection failed to take, I tried again”. Again, no tumour grew. The mouse was eventually given five injections without succumbing to cancer. “I had never seen anything like this”, says Cui. “I was injecting an MHC-negative tumour that normally grows in all mice.” Despite some initial scepticism from colleagues, Cui decided to see if this tumour resistance could be passed on to the offspring of his original failed experiment. To his surprise, the resistance segregated as a dominant trait and Cui now has a colony of 700 mice that carries the trait, which provides resistance to all tumour cell lines so far tested (Proc Natl Acad Sci USA, published online April 30; doi:10.1073/pnas.1031601100). “The clincher for me”, continues Cui, “came when we videotaped leukocytes from
328
Courtesy of Z Cui
Mouse fights cancer with innate immunity
Scanning electron micrograph of an immune cell attacking a cancer cell.
resistant animals attacking tumour cells in vitro”. The tumour cells just popped open, he says, while the normal cells remained unscathed (www.wfubmc. edu/pathology/research/srmouse.htm). The researchers are now trying to
identify which immune cells are responsible for tumour-cell killing and how they recognise the malignant cells. “This is highly original, unexpected and potentially exciting work”, comments Mark Smyth (Peter MacCallum Cancer Institute, Melbourne, Australia). He adds that it is now critical to identify the gene that provides resistance and to see whether spontaneous tumours can develop in the resistant mice. By determining exactly how the innate immune system recognises cancers, it may be possible to develop a new immunological strategy for the treatment of advanced tumours, conclude Smyth and Cui. Jane Bradbury
New boost for Italian cancer research Italy spends 1·1% of their GDP on research compared with around 2% in France, Germany and Britain. “Government financing for biological and biomedical research is laughable”, comments Pier Paolo Di Fiore, director of the Institute for Molecular Medicine (IFOM). “Basically we all live off grants given by a few major charities.” But, the opening of a new cancer research centre in Milan in early April, may prove to be the stimulus Italian research has been waiting for. The IFOM was created by Italy’s largest biomedical research charity the Foundation for Cancer Research (FIRC). The centre will employ around 300 researchers and concentrate on nanotechnology, bioinformatics, and structural biology. FIRC will provide equipment and salaries for infrastructure and common services in Italy, whereas research institutes including the European Institute of Oncology, and Mario Negri Pharmacological Research Institute will provide personnel. The facilities will subsequently be opened to other oncology centres across Italy. “Instead of one or two groups in federal institutions, we will end up with 20 groups working in similar fields who all have access to state-of-
the-art equipment and know-how for post-genomic research”, says Di Fiore. Another problem that has plagued Italian cancer research is fragmentation, a phenomenon Di Fiore attributes to the lack of a central grant awarding agency. “Varying initiatives start from the Health Ministry, Research Ministry, National Research Council, Industry Ministry, etc. So it is very difficult to know how much money is given and what the criteria are...most financing still follows semi-obscure reviewing processes.” He argues that concentrating research facilities is an attempt to compensate for these handicaps and prevent young researchers leaving for other countries. “We need to focus science in a few very good centres”, comments Marco Presta, Brescia University, Italy. However, he fears that these investments will exacerbate the funding shortage in university laboratories: “The risk is that in 10 years time a few excellent places will be islands in a sea of mediocrity.” Di Fiore concurs: “You cannot just build research by financing excellence, you’ve got to finance the whole network, including the small labs that do the training. That can only happen with government money.” Claudia Orellana
THE LANCET Oncology Vol 4 June 2003
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.