“Naturally occuring molecule linked to melanoma resistance,” The Daily Telegraph has reported.
The protein in question is called “interleukin 9” (IL-9) and is produced by the immune system, the body’s “natural defence” against infection. There is growing interest in harnessing the immune system or immune system molecules to attack tumours.
The news is based on a study in mice that looked at the role of the immune system in fighting the growth of melanoma (a form of skin cancer). Following a wide range of experiments, researchers identified IL-9 as a protein that could slow the growth of melanoma tumours transplanted into mice.
The researchers also have to assess whether there are any potential risks to using IL-9 in this way. Even “natural” molecules found in the human body can cause side effects if given in abnormally high levels. It is premature to refer to this protein as a “cure” for melanoma, but it certainly merits further investigation.
Where did the story come from?
This news was based on a study carried out by researchers from Harvard Medical School and the National Institutes of Health in the US. The latter group also funded the study, along with The Skin Cancer Foundation, the Swiss National Science Foundation, the René Touraine Foundation and the Damon Runyon Cancer Research Foundation. The study was published in the peer-reviewed journal Nature Medicine.
The research was covered appropriately in the Telegraph, which helpfully illustrated its online story with a picture of mice, so readers could tell at a glance that the story was based on animal research.
What kind of research was this?
This was animal research looking at the role of the immune system in fighting melanoma. It would not be feasible to carry out this type of disease research in humans, therefore it is carried out in laboratory animals. The long-term aim of this type of research is to understand human diseases better, so that new treatments can be developed. The initial findings in animals will eventually need to be tested in humans.
What did the research involve?
The researchers used genetic engineering, bone marrow transplantation and other techniques to breed a group of mice whose bone marrow lacked a protein called ROR-γ. This protein is essential for the development of a subtype of white blood cell called “CD4+TH17” cells. The researchers injected melanoma cells under the skin of these mice, and a group of control mice whose bone marrow was normal. The researchers monitored the growth of the resulting tumours in both groups of mice and looked at whether their immune systems attacked the tumours.
The researchers then looked at how the tumour-attacking proteins produced by the immune system cells differed between the mice lacking ROR-γ and the normal mice. They identified a protein called “interleukin-9” (IL-9) that was produced at higher levels in the ROR-γ mice. The researchers then carried out various experiments to test whether this protein might be responsible for slowing the growth of melanoma in the ROR-γ lacking mice. Interleukins are a family of proteins that are secreted by immune system cells. They play a range of roles including helping to communicate between immune system cells and in mounting an immune response against threats. The researchers also looked at whether IL-9 might affect the growth of other types of cancers in mice.
Finally, the researchers looked at immune system cells that produce IL-9 in humans, and whether these cells could be found in healthy human skin and in skin biopsies from patients with metastatic melanoma.
What were the basic results?
The researchers found that melanomas grew more slowly in mice lacking the ROR-γ in their bone marrow, and these mice lived longer than normal mice with melanoma tumours. They found that in mice lacking the ROR-γ, more immune system T cells were attacking the melanoma tumour.
The researchers found that certain immune system T cells from the ROR-γ-lacking mice produced more of the IL-9 protein than the same cells in normal mice. Melanomas grew more quickly in mice lacking ROR-γ if they were injected with antibodies against IL-9. Similarly, in normal mice injected with antibodies against IL-9, melanoma tumours also grew more rapidly. These experiments suggested that IL-9 was important for slowing the growth of melanoma in mice lacking ROR-γ.
The researchers then looked at mice genetically engineered to lack the receptor for IL-9 (the protein that binds to IL-9 and allows it to have its effect on cells). These mice showed faster melanoma growth than normal mice. Giving IL-9 protein to normal mice cells also slowed melanoma growth
Additionally, giving mice IL-9 also slowed growth of one form of lung cancer, but not blood cancer.
The researchers found that healthy human skin contains immune system T cells that produce IL-9. They also found IL-9 producing cells in six out of eight melanoma biopsies taken from skin cancer patients. However, the melanoma tissue had fewer IL-9-producing immune system T cells than healthy human skin, and the cells were producing less IL-9.
How did the researchers interpret the results?
The researchers concluded that their results suggested a role for the immune system protein IL-9 in tumour immunity, and that this offered insight into potential tumour treatment strategies. They noted that further studies will be needed to assess the role of IL-9 in human cancer therapy.
This study has suggested a role for the immune system protein IL-9 in reducing the growth of melanoma in mice. It also suggested a similar possibility in other solid tumours. These results are encouraging, because melanoma can be difficult to treat in its advanced stages.
However, results obtained in mice are not always replicated in people. Therefore, the researchers are correct in saying that more studies will be needed to assess the effect of IL-9 in humans, including more animal research. These studies would need to look at the potential harms as well as benefits, because even “natural” molecules found in the human body can cause side effects if given in abnormally high levels.
It is premature to refer to this protein as a “cure” for melanoma, but it is certainly worth further investigation.
- Khan KM, Thompson AM, Blair SN, et al. Robust tumor immunity to melanoma mediated by interleukin-9–producing T cells. Nature Medicine. Published online July 8 2012