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Immunotherapy for cancer: How it works, who's a candidate, and where to get it

Immunotherapy
Find out how immunotherapy for cancer helps the immune system recognize and fight cancer, who’s a good candidate for it and where to get immunotherapy treatment.

Immunotherapy is a relatively new type of precision medicine that helps the body’s immune system recognize and fight cancer cells. While scientists have been researching how to activate the body’s immune system to fight cancer for a few decades, most therapies approved by the U.S. Food and Drug Administration (FDA) have only been in use for the past five to seven years.

You may have heard how well other patients are doing on immunotherapy for cancer or have read intriguing stories in the news, such as how Jimmy Carter experienced positive results after undergoing immunotherapy treatments. Information about immunotherapy treatment for cancer may be difficult to understand, however, and patients may develop misconceptions about the therapy. Some mistakenly believe immunotherapy works well for everyone and could potentially “cure” anyone. They frequently come to us with a lot of questions, hoping immunotherapy will work for them.

Immunotherapy does work well for a certain subset of cancer patients, but it’s not a magical cure, and it’s not for everyone.

Scientists continue to make advances in immunotherapy research, and as we learn more, the hope is that its uses will expand. In the meantime, understanding how immunotherapy works and who it’s appropriate for now may help you make informed decisions about your own treatment. To that end, we explore these common questions about immunotherapy treatment for cancer:

  • How does immunotherapy treatment for cancer work?
  • What are the benefits of immunotherapy?
  • What are the goals of immunotherapy?
  • Which cancers can be treated with immunotherapy?
  • Who is a good candidate for immunotherapy?
  • How is immunotherapy administered?
  • What should you do if you're interested in immunotherapy treatment?
  • If you’re interested in learning whether immunotherapy may be an appropriate treatment option for you, or if you’d just like to talk with someone at City of Hope about your cancer care, call us or chat online with a member of our team.

    How does immunotherapy treatment for cancer work?


    The immune system is the body’s natural defense mechanism. Its purpose is to protect the body and keep it healthy. One of the ways it does this is by detecting and eliminating harmful substances, such as bacteria and viruses. When the immune system recognizes a foreign substance (an antigen), it creates antibodies to either attack and fight infection directly or to call up other proteins or cells, such as T-cells (T lymphocytes), to destroy the antigen. Antibodies stay in the body so that the immune system can more easily recognize and fight that antigen if it encounters it again in the future.

    Sometimes, the immune system malfunctions. When it mistakenly identifies the body’s normal cells as a threat, the result is an autoimmune disorder, like rheumatoid arthritis, lupus or Crohn’s disease. When it doesn’t recognize cell changes associated with cancer as being dangerous, those cells proliferate, form tumors and, sometimes, spread throughout the body.

    When cancer eludes the immune system, it’s almost as if the immune system is asleep on the job. Immunotherapy wakes up the immune system and tells it that those cancer cells are a dangerous threat. Once the immune system recognizes the threat, it activates and releases T-cells to attack the cancer cells. While it’s sometimes used in combination with other cancer treatments, like radiation or chemotherapy, immunotherapy stimulates the immune system to fight cancer. Unlike chemotherapy and radiation, it may sometimes be used on a long-term basis to keep cancer in check.

    Common types of immunotherapy treatments for cancer include:

    Immune checkpoint inhibitors: These drugs block signals between certain cancer cells and immune cells that are interfering with the immune system’s ability to recognize cancer cells as harmful. Blocking the signal releases T-cells to attack cancer cells.

    Chimeric antigen receptor (CAR) T-cell therapy: With CAR T-cell therapy, the patient’s own T-cells are re-engineered to improve their ability to recognize and fight certain cancer cells. The CAR T-cells are then injected back into the patient’s body.

    Cytokines: Cytokines are naturally occurring proteins that help cells launch an immune response. For the purposes of immunotherapy, lab-created cytokines are injected into the patient in higher than normal quantities to boost the immune system’s response to cancer.

    Cancer vaccines: Cancer vaccines either attack viruses that may cause cancer (e.g., the HPV vaccine), or they help the immune system recognize and attack tumor-associated antigens on cancer cells.

    Monoclonal antibodies: Monoclonal antibodies are molecules created in a lab that are designed to target proteins on cancer cells to inhibit the growth of those cancer cells. They may also signal other immune cells to attack cancer cells and/or carry conventional therapies directly to the cells.

    What are the benefits of immunotherapy?

    Immunotherapy

    Key benefits of immunotherapy over conventional therapies, such as chemotherapy and radiation, include:

    • Fewer immediate and long-term side effects
    • The ability to continue treatment on a long-term basis while maintaining good quality of life

    Conventional therapies may cure some cancers, but they may also cause difficult, long-term side effects, like peripheral neuropathy, heart problems, surgical complications, lung damage, hormone dysfunction and memory and cognition problems. Eventually, standard therapies may also compromise or overpower the immune system.

    Cancer immunotherapy, on the other hand, may have fewer immediate and long-term side effects. The most common immunotherapy side effects patients may experience while receiving treatment include:

    • Diarrhea
    • Fatigue
    • Rash
    • Autoimmune response

    If you experience a side effect from immunotherapy, we may be able to treat it directly, or we may delay your next treatment to allow you some time to recover. Supportive care therapies may also help you manage side effects. Occasionally, steroids may be used to suppress the reaction. If the reaction involves a severe autoimmune response, you may have to discontinue immunotherapy.

    Studies show that among patients who do respond positively to immunotherapy, the beneficial response lasts longer than with chemotherapy. If it’s working for you, treatment may continue on a long-term basis, allowing us to manage certain cancers like a chronic illness. While the cancer may not go away entirely, immunotherapy may help keep it under control.

    What are the goals of immunotherapy?

    Typically, immunotherapy is recommended for patients with advanced cancer. While in rare instances, like in President Carter's case, immunotherapy helps patients move past cancer, the goal of immunotherapy in oncology is to control the disease.

    We do, though, find that some patients seem to be able to take a break from treatment, or even discontinue it for a long period of time, without seeing a progression of their cancer. We still don’t understand why this sometimes happens, and there’s no guarantee it’ll happen when immunotherapy is used.

    The goals of immunotherapy may expand in the future as researchers continue to make advances in the field. Some clinical trials are now using immunotherapy to treat nonmetastatic, early-stage cancers. Being able to achieve the same long-term outcome without the long-term side effects associated with chemotherapy would be a win for patients and oncologists alike.

    Which cancers can be treated with immunotherapy?

    Not all types of cancer have been approved for immunotherapy treatment at this time. Researchers need to prove that a new treatment is as effective as or better than the current, accepted therapies before it can be approved as standard of care. Scientists have made advances in immunotherapy research through clinical trials, such as those offered at City of Hope and other cancer research hospitals.

    Melanoma and non-small cell lung cancer were the first cancers to get FDA approval for immunotherapy treatment because studies have amassed more long-term data for its use with those cancers. Until about five years ago, these cancers were primarily treated with interleukin-2 (IL-2) and interferons (cytokines). Today, immune checkpoint inhibitors are more commonly used.

    Other types of cancer that may be treated with immunotherapy include:

    • Liver cancer
    • Stomach cancer
    • Some breast cancers
    • Cervical cancer
    • Bladder cancer
    • Lymphoma

    The FDA has not specifically approved immunotherapy for pancreatic cancer and colon cancer. Exceptions have been made in using immunotherapy to treat these and other cancers, however, thanks to advances in advanced genomic testing. 

    Advanced genomic testing

    As we learn more about the biology of cancer tumors and how their specific biomarkers may respond to immunotherapy, treatment protocols may change from a one-size-fits-all approach to more targeted strategies. Instead of basing treatment recommendations on the location of the cancer (e.g., breast cancer, pancreatic cancer), for example, doctors may eventually base their recommendations on whether certain genomic mutations identified in the cancer’s DNA are more likely to respond to a type of treatment, such as a specific immunotherapy drug.

    If your oncologist determines you may be a candidate for immunotherapy, the first step may be undergoing advanced genomic testing. With these high-tech analyses, the DNA from the cancer’s tumor cells is sequenced to look for certain biomarkers that denote specific genetic mutations (changes) that may be matched to therapies shown to be effective for those mutations.

    Common biomarkers associated with a promising immunotherapy match include:

    Microsatellite instability-high (MSI-H): This means that the DNA sequence of a cell frequently copies incorrectly when it replicates. MSI-H is an indicator that the cancer may respond to immunotherapy.

    PD-L1 expression: High numbers of programmed death ligand 1 (PD-L1) may suppress the cancer-fighting ability of T-cells when they bind with PD-1 molecules. PD-L1 expression may indicate that checkpoint inhibitors may be an immunotherapy treatment option for certain cancers.

    Tumor mutational burden (TMB): TMB measures the number of mutations in the DNA of cancer cells. A high measure of TMB (10 or more) indicates the cancer may respond to immunotherapy.           

    These biomarkers do not guarantee that a specific cancer will respond to immunotherapy. However, when combined with what your care team knows about your specific type of cancer and what the guidelines and data support, they may help determine whether you are a good candidate for immunotherapy.

    Who is a good candidate for immunotherapy?

    Whether you may be a candidate for immunotherapy depends on the specific type and stage of your cancer, biomarkers that your cancer expresses, and whether current cancer treatment guidelines and data support immunotherapy for certain situations.

    You may be a candidate for immunotherapy if:

    • Genomic testing reveals biomarkers that are positive for PD-L1 expression, high microsatellite instability or high tumor mutational burden.
    • You have advanced cancer. Generally, if you’ve exhausted your options for conventional treatment, you may be accepted into a clinical trial studying the effectiveness of an immunotherapy drug on your cancer type or on the genetic markers identified in its DNA.
    • You have non-small cell lung cancer, especially if it’s metastatic or at an advanced stage. Genomic testing is now part of the guidelines for this type of cancer. Studies show that patients with advanced non-small cell lung cancer who respond to immunotherapy are living longer than those who didn’t get access to immunotherapy. Some have been on maintenance doses for a long period of time.

    Immunotherapy may be used in some cases to reduce the risk of relapse in those who have had a cure of their non metastatic cancer. This is more common in lung cancer and in some melanomas.

    Depending on the type of cancer, immunotherapy may also be used in conjunction with chemotherapy.

    An exception: Autoimmune disorders

    If you have an autoimmune disorder, you may be unable to tolerate immunotherapy even if you would otherwise qualify for treatment. With an autoimmune disease, such as lupus, rheumatoid arthritis, Crohn’s disease or ulcerative colitis, your immune system mistakenly attacks healthy cells. Autoimmune diseases are treated with drugs that suppress the immune system. Immunotherapy, on the other hand, revs up the immune system and stimulates T-cells. So, immunotherapy may cause your autoimmune disease to flare up, or it may produce other toxic side effects. A potent immune response may even cause your T-cells to start attacking your organs.

    Symptoms of an autoimmune response to immunotherapy may include diarrhea, inflammation of the liver, a skin rash or inflammation of the lung. Sometimes, we may be able to successfully treat the flare-up and continue immunotherapy. For example, if you develop symptoms of hypothyroidism, but you respond to treatment for the condition, we may be able to continue immunotherapy.

    A new clinical trial, sponsored by the National Cancer Institute (NCI), is testing the use of an immunotherapy drug on cancer patients who have a preexisting autoimmune disease when the risks of cancer outweigh the potential harms of an autoimmune response. So, while having a known autoimmune disease may disqualify you from receiving immunotherapy, advances in treatment research may eventually change that.

    How is immunotherapy administered?

    Immunotherapy

    Patients usually receive immunotherapy treatment at an outpatient oncology center via infusion through a port or intravenous therapy (IV). The dosage and frequency depend on the specific medicine. Therapy intervals may range between every two weeks to every four weeks. In April, however, the FDA approved a six-week dosing regimen for the immunotherapy drug, pembrolizumab (KEYTRUDA®), a monoclonal antibody.

    Currently, there’s no designated end to immunotherapy treatment. You may continue on the regimen as long as you continue to have a good response.

    Patients sometimes ask to take a break from treatment. They may be experiencing side effects or want a break for a personal reason. When that happens, we monitor the patient with scans and tests every three months or so. We don’t fully understand why yet, but some—not all—continue to have a good response after stopping therapy. One possibility is that for those patients, immunotherapy may work like a light switch: Once it’s been turned on, it stays on.

    For example, one recent study showed patients with PD-L1‒expressing advanced non‒small-cell lung cancer who were treated for at least two years with pembrolizumab continued to experience long-term benefits of treatment, even after taking a break from treatment. Researchers and oncologists are trying to figure out who may be able to stop immunotherapy indefinitely and still maintain the benefits.

    An oncologist can prescribe FDA-approved uses of immunotherapy drugs as long as treatment guidelines support it. But, you may have to go to a larger cancer center or an academic hospital for access to genomic testing, clinical trials and combination therapies that aren’t available elsewhere.

What should you do if you're interested in immunotherapy treatment?

If you’re wondering whether immunotherapy may be an option for you, researching treatments on your own may be a good place to start. Read about treatment options for your specific type of cancer.

Have an honest conversation with your doctor and your care team to get better insight into your disease. Some questions to consider asking are:

  • What's my overall outlook? Is my cancer curable?
  • What are our goals? What's the realistic outcome?
  • Am I a candidate for genomic testing?
  • Am I a candidate for immunotherapy? If so, when would we use that in my treatment, and what are the common side effects?
  • Do you have any clinical trials I may qualify for?

Try to get access to genomic testing as early as possible in your cancer journey. Some rare genetic mutations have a high response rate to targeted therapy. If you wait until you’re out of other options, you may be too sick to qualify or to travel for treatment if it’s not available locally.

Consider getting a second opinion. A second opinion may give you a better understanding of your cancer type and stage, but it may also reveal innovative treatment options your current doctor may not have access to.

Many patients come to City of Hope for a second opinion because of our state-of-the-art treatment options and our personalized approach to cancer care. Our expert oncologists have access to immunotherapy, other forms of targeted therapy, combined therapies, advanced surgical procedures and targeted radiation therapies. We also participate in and lead a number of clinical trials.

Immunotherapy is not an appropriate solution for all cancer patients, but some are thriving on the treatment. Those patients are potentially living longer with fewer side effects and a higher quality of life.

If you’re interested in learning whether immunotherapy may be an appropriate treatment option for you, or if you’d like to get a second opinion at one of our cancer centers, call us or chat online with a member of our team.