Scientists have discovered a potential way to improve chemotherapy’s effect on ovarian cancer by manipulating specific immune cells around the tumour.
This advance, led by Dr Samar Elorbany, Professor Fran Balkwill and their team at the Barts Cancer Institute, Queen Mary University of London, could offer a way to help thousands of women with ovarian cancer benefit more from standard therapies and potentially delay relapses.
Ovarian cancer remains one of the most difficult cancers to treat. Around 7,500 women are newly diagnosed with ovarian cancer every year in the UK, but only around 15 per cent of women with the most common type – high-grade serous ovarian cancer (HGSOC) – survive beyond 10 years.
Chemotherapy has been the cornerstone of treatment for decades, but around 80 per cent of women with HGSOC will see their cancer return within two years. When it does, the cancer often develops resistance to further chemotherapy. PARP inhibitors have helped some of those whose tumour carries certain genetic alterations, but these treatments are linked to mutations found in less than 50 per cent of patients.
“The big question is: how can we extend the effectiveness of existing treatments?” said Dr Samar Elorbany, Clinical Lecturer at the BCI and lead author of the study, published in Nature Communications. “In other cancers such as melanoma, new immune therapies have transformed an incurable condition into one that can be successfully treated. We haven’t yet achieved this in ovarian cancer – I want to understand how we can replicate that success for gynaeoncology patients.”
Historically, researchers have focussed on how chemotherapy acts directly on tumour cells. But today, we recognise that treatments have complex helpful and harmful effects on the ‘microenvironment’ of non-cancerous tissue and cells that surrounds the tumour, including immune cells. “Nothing is entirely good or bad – chemotherapy has both pro-tumour and anti-tumour effects,” Dr Elorbany explains. “We wanted to find out what the pro-tumour effect is, so we can block it to improve response to chemotherapy, prolong survival, and reduce the risk of relapse.”
Illuminating the role of chemotherapy on immune cells
Using single-cell RNA sequencing – a cutting-edge method that reveals what thousands of individual cells are doing at one time – Dr Elorbany and colleagues analysed immune cells from patient samples before and after chemotherapy.
When the researchers looked closely at macrophages, a type of immune cell that digests harmful cells and debris, they found that a protein called stabilin-1 (STAB1) becomes more abundant after chemotherapy. This was linked to these cells behaving in a more tumour-friendly manner. By blocking STAB1 in their laboratory models, the team saw a shift towards more tumour-fighting behaviour among the macrophages.
The team also noticed an effect on regulatory T cells (Tregs), which normally suppress other immune cells. They discovered that chemotherapy boosted the number of Tregs within the tumour, potentially reining in the immune system’s ability to attack the cancer. Selectively inhibiting FOXP3 – the master switch for this cell type – resulted in more active and aggressive T cells that were better at killing cancer.
A promising way to extend ovarian cancer survival
These new insights reveal how chemotherapy can inadvertently reinforce tumour-friendly immune signals in ovarian cancer. By redirecting the immune system – using approaches that block STAB1 and FOXP3 – the researchers extended survival in mice with ovarian cancer. In some cases, the mice remained tumour-free even when cancer cells were reintroduced, pointing to an immune ‘memory’ effect.
Dr Elorbany and colleagues are now looking to translate their findings into benefits for patients through clinical trials. Drugs that inhibit stabilin-1 and FOXP3 have been tested in early-stage trials, including in a small number of people with ovarian cancer, but the team’s work shows that using the right combination of drugs with the right timing will be critical if future larger trials are to be successful.
“As a clinician, I see firsthand the limitations our patients face with current therapies. We took those questions to the lab, tested our ideas, and I’m excited that we can now work to bring these insights back to the clinic,” Dr Elorbany said. “Further research is now needed, but we hope our findings pave the way towards better, longer-lasting responses for women with ovarian cancer.”
The work was made possible thanks to funding from Wellbeing for Women, Cancer Research UK and UKRI.
