Key genes have been identified that could help clinicians understand why some ovarian cancer patients respond better to treatment than others, British researchers have announced.
Researchers at Imperial College London have discovered that women whose high-grade serious ovarian cancer (HGSOC) contain tertiary lymphoid structures (TLS) have a significantly better prognosis than others.
Writing in Cell Reports Medicine, the team also reveal they identified genes in HGSOC that are important for TLS formation and function.
When they analysed tumours from 242 HGSOC patients before treatment and compared them to progression free survival rates, women who had TLS in their tumours had a significantly better outcome.
Lead researcher Dr Haonan Lu, of Imperial College’s Department of Surgery and Cancer, said: “People tend to think of all cancer cell activity as purely malignant – but the reality is less clear-cut. 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.”
The team pinpointed the relevant genetic mutations involved in the cancer’s TLS formation, some of which are known to have immune-suppressing functions.
They found that copy mutations in the genes IL15 and CXCL10 in HGSOC can inhibit the lymphoid tissue forming, and that another set of genes, including DCAF15, plays a role in interacting with the TLS tissues after they have been formed, which is likely to make them either 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 team also used artificial intelligence (AI) to develop a potential method of identifying patients with high levels of TLS more quickly compared with standard CT scans.
Professor Eric Aboagye, professor of cancer pharmacology & 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.”
Lu H, Lou H, Wengert G et al. Tumour and local lymphoid tissue interaction determines prognosis in high grade serous ovarian cancer. Cell Reports Medicine 21 June 2023.
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