Scientists have discovered that a well-known protein, when produced by ovarian cancer cells, protects them from being killed by the immune system. This might apply to other kinds of cancer as well, opening doors to new immunotherapies and hopefully helping in the fight against cancer.
What makes us distinct from one another, from an immunological point of view, is a group of genes called HLA. They are varied across the human population and it is these genes that need to be tested and perfectly matched when looking for a transplant donor. One of them, called HLA-E, seems to also have a role in cancer, and this role is good for the cancer, bad for the patient. Marloes Gooden and colleagues made this discovery in ovarian cancers (1), which are usually diagnosed quite late and have poor prognosis, as only about one in two diagnosed women will live longer than 5 years.
Any cancer that arises in our body can be recognised and attacked by the immune system. In turn, the cancer cells can develop some strategies to evade the immune response and HLA-E production seems to be one of these strategies. Cancer masses are often infiltrated by immune system cells called cytotoxic T lymphocytes, or CTLs. They act a little bit like very aggressive policemen who chase and kill criminals. CTLs have the natural ability to recognise and kill any cell that doesn’t appear normal, which in this case are cervical cancer cells. But when a cancer cell produces this HLA-E protein, it seems to be functioning as an anti-CTL taser. The CTL is still there, in the tumour, and even though it might be able to “see” the nasty cancer cell, HLA-E makes it not do nothing about it.
The researchers analysed ovarian cancer samples from hundreds of patients, many of whom already died. When they looked at the amount of CTLs in the samples it became pretty evident that the more CTLs infiltrate the cancer (the more policemen chase the criminals), the longer the patient will live. But the picture didn’t seem quite complete at that stage. They decided to divide the cancer samples into two groups: one where the HLA-E levels were very low or even undetectable, and one where they were high or very high. In the first group they made a similar finding: the more CTLs infiltrated the cancer mass the longer the patient lived, and the difference in survival was even more evident. But when they looked at the patients with high HLA-E levels in the cancer cells, it turned out that the number of infiltrating CTLs did not make any difference to how long the patients would live.
The authors do mention that they stumbled upon more molecules that might be connected with this whole phenomenon, but just discovering this important function for HLA-E is an important piece of the puzzle. There are currently quite a lot of established and experimental therapies for cancer called monoclonal antibody therapies. They way they work, is by giving the patient antibodies against molecules that seem to facilitate cancer survival and aggressiveness. The study mentioned here might have identified one of these molecules and hopefully, in the future, new anti-HLA-E therapies will let women with ovarian cancer live much longer.
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