Tag Archives: immunotherapy

Immune targets for chemotherapy-resistant breast cancers identified

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Scientists have identified immune cell types 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, with support from Breast Cancer Now, have performed a deep dive into the different immune markers within tumour tissues and blood samples of early breast cancer patients whose cancer failed to respond to chemotherapy given to them prior to surgery.

The research, published today in Clinical Cancer Research, a journal of the American Association for Cancer Research, gives insight into the function of immune cells in patients with chemotherapy-resistant breast cancers. While chemotherapy may not kill cancer cells in these high-risk patients, immunotherapy, a type of treatment that helps the immune system to attack cancer cells, may provide a benefit.

To investigate the immune environment that surrounds these chemotherapy resistant tumours, researchers employed multiple and novel complementary technologies looking at proteins and genes on both pre-treatment and post-treatment breast cancer tissue. They also measured how 1,330 cancer and immune-related genes within cancer tissues were affected by chemotherapy.

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They found that chemotherapy resistant cancer cells had very few immune cells around them, but chemotherapy did induce changes in several immune cell types. 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 to fight infection and cancer. But analysis found the increased NK cells in patients with chemotherapy resistant disease lacked cytotoxic activity – the ‘killing instinct’.

Researchers also found immune-related genes associated with NK cells were those associated with cell inhibition or exhaustion, which meant NK cells were unable to fight cancer cells. This new insight into the behaviour of NK cells could be used to develop specific immunotherapies for these high-risk patients. This would need to be investigated in future clinical trials.

These findings also show that blood monitoring during chemotherapy may help predict chemotherapy response early, potentially allow for tailoring of treatment 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.”

chemotherapy

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.”

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.”

Some cancer immunotherapy treatments may damage fertility, women’s hormonal health

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Researchers have discovered that some immunotherapy treatments used to treat cancer can cause fertility damage.

It means these treatments could affect the future fertility and hormonal health of female cancer survivors, prompting experts to call for more research and preventative measures, such as freezing eggs.

Led by the Biomedicine Discovery Institute at Monash University and the Peter MacCallum Cancer Centre, the pre-clinical trial showed that immune checkpoint inhibitors, a common type of immunotherapy drug, resulted in permanent damage to mouse ovaries and the eggs stored inside.

cancer/photo:en.wikipedia.org

Traditional cancer therapies, such as chemotherapy and radiotherapy, are already linked to permanent, negative side effects on the ovaries. This can lead to infertility and premature menopause in young girls and women.

Researchers found that checkpoint inhibitor immunotherapy reduced the number and quality of their eggs, interfered with ovulation, and disrupted the fertility cycle.

Until now the potential fertility side effects of immunotherapy, an emerging and increasingly common cancer treatment that stimulates the immune system, have been unknown.

The study found that a type of immunotherapy called immune checkpoint inhibitors, which ‘release the brakes’ on the immune system to enhance a patient’s ability to fight cancer, could impair immediate and future fertility.

Its authors said studies in female patients were now needed to investigate the findings. In the meantime, fertility preservation through egg or embryo freezing should be considered for women using these immunotherapies.

“Initially these treatments were thought to be less damaging (than chemo and radiotherapy) in the context of off-target effects to the body in general,” Ms Alesi said. “However, it is now clear that inflammatory side effects in other organ systems are quite common with these drugs.

“Our study highlights that caution should be exercised by clinicians and their patients, for whom fertility may be a concern. Studies in women receiving these drugs must now be prioritised.”

Peter MacCallum Cancer Centre Specialist Medical Oncologist Professor in breast cancer and a senior author on the study Sherene Loi said further research into how these drugs impact the ovarian function and fertility of women receiving these drugs must be prioritised and should be included in future clinical trials involving women of reproductive age.

“Our study further highlights that fertility discussions are critical for all age appropriate women who are recommended to receive chemotherapy as well as immunotherapy,” Professor Loi said.

“Appropriate interventions that can preserve fertility and ovarian function can be implemented to facilitate pregnancies in the future, post completion of treatment. These interventions need to be implemented in a timely manner, so as not to delay anti-cancer treatment.

“Immunotherapy is now becoming a standard of care for many women with curable early stage breast cancer, due to impressive results in reducing breast cancer recurrences, but further research into the long-term effects of immunotherapy is needed.”

Apart from drugs that block ovaries from producing hormones during chemotherapy, and strategies to prevent premature menopause in younger women, Ms Alesi said egg and embryo freezing was the only fertility preservation measure available.

She said it was important to remember that embryo freezing was expensive, invasive and did not prevent ovarian damage. This meant that premature menopause could still be a risk for these women.

“Therefore, we are now prioritising investigation of targeted ovarian preservation strategies that aim to prevent the damage to the ovary from occurring in the first place, without interfering with the drugs’ ability to fight the cancer” she said.