Researchers have identified a group of immune cells that could be targeted to develop new treatments for breast cancers that are resistant to chemotherapy.

Scientist working in a lab

Researchers, part-funded by Breast Cancer Now, investigated the features of tumours and blood samples of early breast cancer patients whose cancer didn’t respond to chemotherapy given to them before surgery.

This new research provides important information about the immune system in and around these tumours. While chemotherapy doesn’t work well to treat these cancers, immunotherapy, a type of treatment that helps the immune system to recognise and destroy cancer cells, may provide a benefit.

These findings could help to develop new immunotherapy treatments for people whose breast cancer isn’t responding well to chemotherapy.

Understanding chemotherapy resistance

Chemotherapy is a commonly used treatment for breast cancer. However, some breast cancers can become resistant to chemotherapies, which can help breast cancers to come back after treatment.

Dr Sheeba Irshad and her team at King’s College London used cutting-edge techniques look at various proteins and genes in breast cancer tumours before and after chemotherapy to better understand how cancer cells can resist this treatment.

They looked at the type and number of immune cells that surround chemotherapy-resistant tumours and measured 1,330 cancer and immune-related genes that were affected by chemotherapy.

The researchers found that tumours that were resistant to chemotherapy had fewer immune cells, and that chemotherapy influenced several types of immune cells in these tumours.

­Sheeba, who led the study, explained: ‘Chemotherapy resistance in aggressive early breast cancers is a major reason why cancer regrows after treatment, contributing significantly to people not surviving their disease. In order to find the right targets for drug developments, it’s important to have a deep understanding of the complex mechanisms that allow some cancer cells to resist treatment, then hide from our immune system to only re-emerge later when they’re harder to eradicate.’

Discovering targets for new treatments

Sheeba and her team found that there was an increased number of immune cells called neutrophils and natural killer cells around the chemotherapy-resistant cancer cells. These immune cells are part of the first line of defense that help fight infection and cancer. However, they lacked their ‘killing instinct’.

‘Our work has identified several cell types that would be worth investigating further to understand how they are interacting with the resistant cancer cell and how we can tweak that for our benefit. I am excited to continue to investigate these findings further,’ said Sheeba.

The team also noticed that activity of some genes in these immune cells was preventing them from fighting cancer. This insight could be used to develop new immunotherapies.

The researchers also suggest that monitoring patients’ blood during chemotherapy treatment may help them spot early if breast cancer is resisting the treatment and offer alternative treatments.

Dr Kotryna Temcinaite, Senior Research Communications Manager at Breast Cancer Now, added: ‘With an estimated 35,000 people living with incurable secondary (metastatic) breast cancer in the UK, it’s vital we develop smarter, more effective treatments to ensure fewer people hear the devastating news the disease has returned and spread to other parts of the body. This exciting early-stage research helps to lay the groundwork for discovering a way to target breast cancer cells that resist chemotherapy treatment. We hope by building on these findings, scientists will ultimately be able to develop immunotherapy treatments that may help more people survive breast cancer.’

This research was published in the journal Clinical Cancer Research and was funded by Cancer Research UK and Breast Cancer Now.

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