Study finds how immune cells function in patients with chemotherapy-resistant breast cancers

The researchers identified immune cell types that could be targeted to develop specialised immunotherapies in chemotherapy-resistant breast tumours.

Researchers from King’s College London and The Institute of Cancer Research, London, with funding from Breast Cancer Now, investigated the distinct immunological markers found in tumour tissues and blood samples from early breast cancer patients whose cancer did not respond to chemotherapy before surgery. The study, which was published today in Clinical Cancer Research, a journal of the American Association for Cancer Research, sheds light on how immune cells behave in patients with chemotherapy-resistant breast cancer.

While chemotherapy may not eliminate cancer cells in these high-risk patients, immunotherapy, which aids the immune system in attacking cancer cells, may be beneficial.

Researchers used several and unique complementary technologies to examine at proteins and genes on both pre-treatment and post-treatment breast cancer tissue to investigate the immunological milieu that surrounds these chemotherapy-resistant tumours. They also looked at how chemotherapy altered 1,330 cancer and immune-related genes in cancer tissues.

They discovered that chemotherapy-resistant cancer cells were surrounded by very few immune cells, although chemotherapy did cause alterations in several immune cell types. They discovered an increase in the number of “innate” (first responder) cells such neutrophils and natural killer (NK) cells in particular. NK cells aid the body in its battle against infection and cancer. However, the study discovered that the enhanced NK cells in chemotherapy-resistant patients lacked cytotoxic function – the ‘killing instinct.’

Researchers also discovered that immune-related genes linked to NK cells were linked to cell inhibition or exhaustion, implying that NK cells were unable to combat cancer cells. This new understanding of NK cell behaviour could be leveraged to build targeted immunotherapies for these high-risk patients. Future clinical trials would need to look into this.

These findings also suggest that blood monitoring throughout chemotherapy may aid in early prediction of chemotherapy response, thus allowing for treatment modification prior to surgery.

Lead author Dr Sheeba Irshad, Cancer Research UK Clinician Scientist at King’s College London said: “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.”

“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.”

Professor Andrew Tutt, Director of the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, and of the Breast Cancer Now Research Unit at King’s College London, said: “Great strides have been made in harnessing immunotherapies to treat several types of cancer, but we need to do better to realise their potential for patients with breast cancer.

“This exciting work advances our understanding of the interaction between cancer cells and the immune system during treatment, and why existing treatments work well for some patients, but not others. I hope this research will help us to enhance the anti-cancer immune response in breast cancer, particularly for patients whose cancer has not responded well to chemotherapy.”

Advances in Breast Cancer Treatment

Dr Kotryna Temcinaite, Senior Research Communications Manager at Breast Cancer Now, said: “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, which has been part-funded by Breast Cancer Now, 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.”

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