Ovarian cancer study finds key gene for potential treatment

The new study increases knowledge about why some women with the deadliest forms of ovarian cancer respond better to treatment than others.

Researchers at Imperial College London in England have confirmed that the tumors of some women with high-grade serious ovarian cancer (HGSOC) contain a type of lymphoid tissue – known as tertiary lymphoid structures, or TLS – and the presence of this tissue gives women a much better prognosis. They have also identified genes in HGSOC that are important for TLS formation and function.

The lymphatic system helps fight infection by producing immune cells such as T cells and antibodies. But TLS, which is in some ways similar to ‘normal’ lymphatic tissue, is found by researchers in a wide variety of tumor types.

This study reveals TLS improves outcomes in women with high-grade serious ovarian cancer

By analyzing the tumors of 242 HGSOC patients before treatment and comparing them to progression-free survival rates, the researchers found that women who had TLS in their tumors had significantly better outcomes. The study, published in Cell Reports Medicine, and funded by the National Institute for Health and Care Research Imperial Biomedical Research Center, was one of the first scientists to find TLS in women with high grades of serious ovarian cancer and link it to better outcomes. .

Lead researcher Haonan Lu, from the Department of Surgery and Cancer, said: “People tend to think of all cancer cell activity as purely malignant – but the reality is less clear. Tumors can hijack a number of normal body processes and here, they seem to be hijacking the formation of normal human lymph tissue within him. Some of these lymphoid structures can then mature and activate T cells, which can attack the cancer itself.”

Approximately 7,500 women are diagnosed with HGSOC each year, and because it is often discovered late, many patients experience relapse of the disease, leading to a five-year survival rate below 40%. Currently treated with surgery and chemotherapy.

The team was able to pinpoint relevant genetic mutations involved in the formation of cancerous TLS, some of which are known to have immune suppressive functions. The researchers found that mutational copies of the IL15 and CXCL10 genes in HGSOC can inhibit lymphoid tissue formation. They also found that other sets of genes, including DCAF15, play a role in interacting with the TLS network once it is formed, possibly making it more or less active.

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

Implementing artificial intelligence to identify patients with high levels of TLS

The researchers also, for the first time, developed a potential method for identifying patients with high levels of TLS from standard CT scans, using artificial intelligence (AI). This can ensure that women who would benefit from different treatments are found more quickly.

Although CT scans are part of standard care for the condition, TLS tissue is not visible to the human eye from a normal CT scan. But the research team has developed an AI algorithm that is trained to detect structures within tumors and has successfully tested the algorithm on scans of patients at Hammersmith Hospital, part of the Imperial College Healthcare NHS Trust, with known TLS networks.

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 whether a patient has high or low TLS in the future and treat them accordingly.”

The researchers have 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-tumor immunity for all HGSOC patients, even those without TLS in the tumor.