The researchers discovered immune cell types that could be used to develop specific immunotherapies for chemotherapy-resistant breast cancer.
Researchers from King's College London and The Institute of Cancer Research, London, with funding from Breast Cancer Now, investigated the different immune 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 in Clinical Cancer Research, a journal of the American Association for Cancer Research, sheds light on how immune cells function in patients with chemotherapy-resistant breast cancer.
While chemotherapy may not be effective in killing cancer cells in these high-risk patients, immunotherapy, a type of treatment that aids the immune system in attacking cancer, may be.
Researchers used multiple and novel complementary technologies to look at proteins and genes on both pre-treatment and post-treatment breast cancer tissue to investigate the immune environment that surrounds these chemotherapy-resistant tumours.
They also looked at how chemotherapy affected 1,330 cancer and immune-related genes in cancer tissues.
They discovered that chemotherapy-resistant cancer cells were surrounded by very few immune cells, but chemotherapy did cause changes in several immune cell types.
They discovered an increase in the number of "innate" (first responder) cells like neutrophils and natural killer (NK) cells in particular.
NK cells aid the body in its fight against infection and cancer.
However, the study discovered that the increased NK cells in chemotherapy-resistant patients lacked cytotoxic activity - 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 fight cancer cells.
This new understanding of NK cell behaviour could be used to develop targeted immunotherapies for these high-risk patients.
Future clinical trials would need to look into this.
These findings also suggest that blood monitoring during chemotherapy may aid in early prediction of chemotherapy response, potentially allowing for treatment tailoring prior to surgery.
"Chemotherapy resistance in aggressive early breast cancers is a major reason why cancer regrows after treatment, contributing significantly to people not surviving their disease," said lead author Dr Sheeba Irshad, Cancer Research UK Clinician Scientist at King's College London.
In order to locate the best To find the right targets for drug development, it's critical to understand the complex mechanisms that allow some cancer cells to resist treatment, then hide from our immune system, only to re-emerge later when they're more difficult to eradicate."
Our research has identified several cell types that merit further investigation to better understand how they interact with resistant cancer cells and how we can manipulate that to our advantage.
"I am very excited to continue researching these findings."
"Great strides have been made in breast cancer research," said Professor Andrew Tutt, Director of the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, and the Breast Cancer Now Research Unit at King's College London.
"This exciting work advances our understanding of how cancer cells interact with the immune system during treatment, as well as why existing treatments work well for some patients but not others."
I hope that this research will help us improve the anti-cancer immune response in breast cancer patients, especially those whose cancer has not responded well to chemotherapy."
"With an estimated 35,000 people living with incurable secondary (metastatic) breast cancer in the UK, it's critical we develop smarter, more effective treatments to ensure fewer people hear the devastating news that the disease has returned and spread to other parts of the body," said Dr. Kotryna Temcinaite, Senior Research Communications Manager at Breast Cancer Now.
This exciting early-stage research, which is partially funded by Breast Cancer Now, contributes to
This exciting early-stage research, which has been partially funded by Breast Cancer Now, contributes to the discovery of a method to target breast cancer cells that resist chemotherapy treatment.
We hope that by building on these discoveries, scientists will be able to develop immunotherapy treatments that will allow more people to survive breast cancer."
Very Good Info
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