Scientists have identified types of immune cells that could be targeted to develop specific immunotherapies in chemotherapy-resistant breast cancers.
Researchers from King’s College London and the Institute of Cancer Research London, supported by Breast Cancer Now, have taken a deep dive into different immune markers in tumor tissue and blood samples from early stage breast cancer patients. breast whose cancer did not respond to the given chemotherapy. to them before surgery.
The research, published today in Clinical Cancer Research, a journal of the American Association for Cancer Research, provides insight into the function of immune cells in patients with chemotherapy-resistant breast cancer. While chemotherapy may not kill cancer cells in these high-risk patients, immunotherapy, a type of treatment that helps the immune system attack cancer cells, may provide a benefit.
To investigate the immune environment surrounding these chemotherapy-resistant tumors, the researchers employed multiple and novel complementary technologies that looked at proteins and genes in both pre-treatment and post-treatment breast cancer tissue. They also measured how 1,330 genes related to cancer and the immune system within cancerous tissues were affected by chemotherapy.
They found that chemotherapy-resistant cancer cells had very few immune cells around them, but chemotherapy induced changes in several types of immune cells. Specifically, they found increases in the number of “innate” (first responder) cells such as neutrophils and natural killer (NK) cells. NK cells help the body fight infection and cancer. But the analysis found that increased NK cells in patients with chemotherapy-resistant disease lacked cytotoxic activity – the “killing instinct”.
The researchers also found that the immune-related genes associated with NK cells were those associated with cellular inhibition, or exhaustion, which meant that the NK cells were unable to fight the cells cancerous This new insight into NK cell behavior could be used to develop targeted immunotherapies for these high-risk patients. This should be investigated in future clinical trials.
These findings also show that blood monitoring during chemotherapy can help predict early chemotherapy response, potentially allowing treatment to be tailored before surgery.
Resistance to chemotherapy in early aggressive breast cancers is one of the main reasons why the cancer grows back after treatment, contributing significantly to people not surviving their disease. In order to find the right targets for drug development, it is important to have a deep understanding of the complex mechanisms that allow some cancer cells to resist treatment and then hide from our immune system to re-emerge later when needed more difficult to eradicate. .
Our work has identified several cell types that would be worth further investigation to understand how they are interacting with the resistant cancer cell and how we can adjust this to our benefit. I’m excited to continue investigating these findings further.”
Dr Sheeba Irshad, Lead Author, Cancer Research UK Clinical Scientist, King’s College London
Professor Andrew Tutt, director of the Toby Robins Center for Breast Cancer Research at the Institute of Cancer Research London and the Breast Cancer Research Unit at King’s College London, said: “There have been Great strides have been made in harnessing immunotherapies to treat various types of cancer, but we need to do better to realize their potential for breast cancer patients.
“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 for others. I hope this research will help us to improve the anticancer immune response in breast cancer, especially for patients whose cancer has not responded well to chemotherapy.”
Dr Kotryna Temcinaite, senior director of research communications at Breast Cancer Now, said: “With approximately 35,000 people living with incurable secondary (metastatic) breast cancer in the UK, it is vital that we develop smarter and more effective treatments to ensure fewer people hear the devastating News that 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, is helping to lay the foundations for discover a way to target breast cancer cells that resist chemotherapy treatment.We hope that based on these findings, scientists can develop immunotherapy treatments that can help more people survive breast cancer mom.”
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Journal reference:
Gazinska, P., et al. (2022) Dynamic changes in relevant NK, neutrophil and B cell immunophenotypes in neoadjuvant high metastatic risk chemotherapy-resistant early breast cancers. Clinical cancer research. doi.org/10.1158/1078-0432.CCR-22-0543.