Video: Gene Signature Discovery May Predict Response To Immunotherapy

by NCN Health And Science Team Posted on November 25th, 2018

Houston, Texas, USA : Scientists led by Dr. Daniel De Carvalho at Princess Margaret Cancer Centre have discovered a gene signature biomarker that may predict which patients will respond – or not – to immunotherapy.

Dr. De Carvalho, principal investigator, says the gene signature relates to the body’s molecular network called the extracellular matrix (ECM) that underpins and physically supports cells. For cancer patients with the gene signature, the research suggests the ECM can stiffen around the diseased cells to form a barrier that immune cells simply cannot penetrate.

“The ECM gene signature associated with response to immune therapy is important because as of today we do not have a very good way to predict which patient will respond or which patient will not respond,” says Dr. De Carvalho, Senior Scientist at the cancer centre.

The multi-institutional scientific team used a big data approach and examined available data across thousands of patient samples from many different cancers to find that in some patients the immune cells were not penetrating the tumour, despite the fact these patients had molecular markers that would predict immune response.

“That’s when we started to think that ECM could be playing a role in actually physically blocking the immune system,” Dr. De Carvalho says.

With further experimental study to validate the biomarker, Dr. De Carvalho says the research lays the foundation for a new therapeutic strategy to focus first on ways to disable the ECM to enable immunotherapy.

“The ultimate goal is to find a biomarker that can help the clinician decide if a patient should receive immunotherapy or not,” he says. “For those who will not respond, the answer could be the patient would first receive a drug to target the ECM, and then be able to respond to immune therapy.”

The findings are published in Nature Communications (doi: 10.1038/s41467-018-06654-8).

The research was funded by The Princess Margaret Cancer Foundation, the Cancer Research Society, the Canadian Cancer Society, the Ontario Institute for Cancer Research, a Canada Research Chair and the Canadian Institutes of Health Research.

Video : Dr. Daniel De Carvalho discusses his study published in Nature Communications, which found a gene signature biomarker that may help predict which patients will respond to immune therapy

Video credit : UHN

Immunotherapy to Treat Cancer

Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. The immune system helps your body fight infections and other diseases. It is made up of white blood cells and organs and tissues of the lymph system.

Immunotherapy is a type of biological therapy. Biological therapy is a type of treatment that uses substances made from living organisms to treat cancer.

Types of Immunotherapy

Several types of immunotherapy are used to treat cancer. These treatments can either help the immune system attack the cancer directly or stimulate the immune system in a more general way.

Types of immunotherapy that help the immune system act directly against the cancer include:

Checkpoint inhibitors, which are drugs that help the immune system respond more strongly to a tumor. These drugs work by releasing “brakes” that keep T cells (a type of white blood cell and part of the immune system) from killing cancer cells. These drugs do not target the tumor directly. Instead, they interfere with the ability of cancer cells to avoid immune system attack.

Adoptive cell transfer, which is a treatment that attempts to boost the natural ability of your T cells to fight cancer. In this treatment, T cells are taken from your tumor. Then those that are most active against your cancer are grown in large batches in the lab.

The process of growing your T cells in the lab can take 2 to 8 weeks. During this time, you may have treatments such as chemotherapy and radiation therapy to reduce your immune cells. After these treatments, the T cells that were grown in the lab will be given back to you via a needle in your vein.

Monoclonal antibodies, also known as therapeutic antibodies, which are immune system proteins created in the lab. These antibodies are designed to attach to specific targets found on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system. Other monoclonal antibodies directly stop cancer cells from growing or cause them to self-destruct. Still others carry toxins to cancer cells. Because therapeutic monoclonal antibodies recognize specific proteins on cancer cells, they are also considered targeted therapies.

Treatment vaccines, which work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease.
Types of immunotherapy that enhance the body’s immune response to fight the cancer include:

Cytokines, which are proteins made by your body’s cells. They play important roles in the body’s normal immune responses and also in the immune system’s ability to respond to cancer. The two main types of cytokines used to treat cancer are called interferons and interleukins.
BCG, which stands for Bacillus Calmette-Guérin, is an immunotherapy that is used to treat bladder cancer. It is a weakened form of the bacteria that causes tuberculosis. When inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer.

Who Receives Immunotherapy

Immunotherapy is not yet as widely used as surgery, chemotherapy, and radiation therapy. However, immunotherapies have been approved to treat people with many types of cancer. To learn about immunotherapies that may be used to treat your cancer, see the PDQ® adult cancer treatment summaries and childhood cancer treatment summaries.

Many other immunotherapies are being studied in clinical trials, which are research studies involving people. To find a study that may be an option for you, visit Find a Clinical Trial.

How Immunotherapy Works against Cancer

One reason that cancer cells thrive is because they are able to hide from your immune system. Certain immunotherapies can mark cancer cells so it is easier for the immune system to find and destroy them. Other immunotherapies boost your immune system to work better against cancer.

Immunotherapy Can Cause Side Effects

Immunotherapy can cause side effects, which affect people in different ways. The side effects you may have and how they make you feel will depend on how healthy you are before treatment, your type of cancer, how advanced it is, the type of therapy you are getting, and the dose. Doctors and nurses cannot know for certain how you will feel during treatment.

The most common side effects are skin reactions at the needle site. These side effects include: Pain, Swelling, Soreness, Redness, Itchiness, Rash,

You may have flu-like symptoms, which include: Fever, Chills, Weakness, Dizziness, Nausea or vomiting, Muscle or joint aches, Fatigue, Headache, Trouble breathing, Low or high blood pressure.

Other side effects might include: Swelling and weight gain from retaining fluid, Heart palpitations, Sinus congestion, Diarrhea, Risk of infection.

Immunotherapies may also cause severe or even fatal allergic reactions. However, these reactions are rare.

How Immunotherapy Is Given

Different forms of immunotherapy may be given in different ways. These include:

  • Intravenous (IV)
    The immunotherapy goes directly into a vein.
  • Oral
    The immunotherapy comes in pills or capsules that you swallow.
  • Topical
    The immunotherapy comes in a cream that you rub onto your skin. This type of immunotherapy can be used for very early skin cancer.
  • Intravesical
    The immunotherapy goes directly into the bladder.

Where You Go for Your Immunotherapy Treatment

You may receive immunotherapy in a doctor’s office, clinic, or outpatient unit in a hospital. Outpatient means you do not spend the night in the hospital.

How Often You Will Receive Immunotherapy Treatment

How often and how long you receive immunotherapy depends on:

  • Your type of cancer and how advanced it is
  • The type of immunotherapy you get
  • How your body reacts to treatment

You may have treatment every day, week, or month. Some immunotherapies are given in cycles. A cycle is a period of treatment followed by a period of rest. The rest period gives your body a chance to recover, respond to the immunotherapy, and build new healthy cells.

How to Tell Whether Immunotherapy Is Working

You will see your doctor often. He or she will give you physical exams and ask you how you feel. You will have medical tests, such as blood tests and different types of scans. These tests will measure the size of your tumor and look for changes in your blood work.

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