Ovarian cancer study identifies key genes for potential treatments

A new study has highlighted the unique nature of ovarian cancer and the extent of variability between patients.

The study, conducted by researchers at Imperial College London, has confirmed that the tumours of some women with high-grade serious ovarian cancer (HGSOC) contain a type of lymphoid tissue, known as tertiary lymphoid structures or TLS, of which presence gives women a better prognosis.

They have also identified genes in high-grade serious ovarian cancer that are important for TLS formation and function.

The lymphatic system in our bodies helps fight off infection by producing immune cells such as T cells and antibodies. But TLS, which are in some ways similar to “normal” lymphatic tissues, are being found by researchers in different types of tumours.

By analysing tumours from 242 high-grade serious ovarian cancer patients before treatment and comparing them to progression free survival rates, the researchers found that women that had TLS in their tumours had a significantly better outcome.

The study, published in Cell Reports Medicine and funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre, is one of the first times scientists have found TLS in women with high-grade serious ovarian cancer and linked them to a better outcome.

“People tend to think of all cancer cell activity as purely malignant, but the reality is less clear-cut,” explained lead researcher Dr Haonan Lu, from the Department of Surgery and Cancer.

“Tumours can hijack a number of normal body processes and here, they seem to be hijacking the formation of normal human lymph tissue within themselves. Some of these lymphoid structures are able to then mature and activate T cells, which could attack the cancer itself.”

Around 7,500 women are diagnosed with high-grade serious ovarian cancer each year. Due to late diagnosis, many experience disease relapse, leading to a five-year survival rate of below 40 per cent.

The researchers were able to pinpoint the relevant genetic mutations involved in the cancer’s TLS formation, some of which are known to have immune-suppressing functions.

The team found that copy number mutations in the genes IL15 and CXCL10 in HGSOC can inhibit the lymphoid tissue forming. They also found that another set of genes, including DCAF15, plays a role in interacting with the TLS tissues after they have been formed, probably making them more or less active.

Dr Lu said: “There is great potential for targeting these genes for benefits in ovarian cancer treatment. It’s now becoming clear how the genetic background of the tumour type interacts with a TLS to have more or less TLS function, and that will help us identify potential targets for therapy.”

The scientists have also, for the very first time, developed a potential method of identifying patients with high levels of TLS from standard CT scans, using AI. This could ensure that those women who would benefit from different treatments are found more quickly, they said.

Although CT scans form part of standard treatment of the condition, TLS tissues are not visible to the human eye from a normal CT scan.

However, the research team has developed an AI algorithm that was trained to detect the structures within the tumours and have successfully tested the algorithm on scans of patients at Hammersmith Hospital, known to have TLS tissues.

Professor Eric Aboagye, professor of cancer pharmacology and molecular imaging at Imperial College London, said: “This non-invasive identification test means that oncologists will be able to determine if a patient has high or low TLS in future and treat them accordingly.”

The researchers have now received a project grant from Target Ovarian Cancer to further investigate the relevant genetic mutations identified, and explore whether it is possible to activate anti-tumour immunity for all high-grade serious ovarian cancer patients.