How Immunotherapy Can Treat Cancer and Other Diseases: 8 Things to Know

If you were diagnosed with a serious disease, one of your first questions might be, “How is it treated?” For a growing number of patients, the answer is immunotherapy, which works by using the body’s own immune system to fight the disease.

Immunotherapy has been gaining traction over the years in two areas: cancer and autoimmune diseases. For instance, immunotherapy can help the immune system identify and destroy invading cancer cells. For autoimmune diseases like rheumatoid arthritis (RA) and multiple sclerosis (MS), in which the body mistakenly attacks its own cells—immunotherapy can tamp down the immune system’s power, usually without difficult side effects.

Immunotherapy doesn’t help everyone or every disease, but when it works well, the results can be dramatic. “It’s been absolutely a game-changer,” says David Hafler, MD, chair of the Department of Neurology and an expert on autoimmune diseases, including MS.

Mario Sznol, MD, a Yale Medicine oncologist and co-leader of the Cancer Immunology Program at Yale Cancer Center, agrees and is just as positive about immunotherapy’s use for multiple types of cancer. “We're still a long way from immunotherapy curing cancer without side effects in 100% of patients,” he says. “But even based on what we know today, some patients are getting long, durable responses that would have been impossible in the past."

Below, Drs. Hafler and Sznol help us answer eight questions to help people understand how immunotherapy is making a difference in the treatment of cancer and autoimmune diseases.

The immune system is made up of a group of organs, cells, and proteins that work together to fight off pathogens—a catchall term that refers to disease-causing microbes, including bacteria, viruses, parasites, and fungi. The immune system further protects against toxins that some pathogens produce, and it also detects and kills cells that are infected by a pathogen or have become cancerous. In short, it’s a system that aims to keep you healthy and free of disease by recognizing and eliminating infectious organisms or cells that don't belong in your body.

When the immune system encounters a pathogen for the first time, certain immune cells detect its antigens (the tiny structures that protrude from its surface) and recognize it as a dangerous invader. The immune cells attach to the pathogen and “activate,” producing thousands of copies of themselves, as well as thousands of antibodies.

At this point, the immune cells and antibodies attack and destroy the pathogenic invaders. If any of the body’s cells have been infected, the immune system kills them to stop the pathogen from spreading throughout the body.

Once the pathogen has been cleared, the immune cells and antibodies begin to decline in number. But a few specialized memory cells remain. These cells preserve a record of the pathogen, so if the immune system ever encounters that pathogen again, it can launch a rapid, powerful response against it.

Immunotherapy is an umbrella term that encompasses different approaches to harnessing the immune system to fight disease. This includes widely used therapies that have been employed for years to treat allergies and stop the body from rejecting transplanted organs.

In recent years, research has focused on the use of immunotherapy to treat cancer. Experts know the immune system can work against cancer as it does against the flu, for example—but not as effectively, Dr. Sznol says. “Cancer cells have ways to outsmart the immune system—sometimes by blocking its ability to recognize them. So, we use immunotherapy to modify the immune system in ways that enable it to work better.” The end goal for its use in cancer care is to push the body’s immune system to better identify and destroy the cancer cells, he adds.

For autoimmune diseases, the task is different. There are more than 80 known diseases, including lupus, in which the immune system becomes overactive to the point that it starts mistakenly attacking healthy cells in the body’s organs and tissues. Immunotherapy can suppress—dampen or put the brakes on—an overactive immune system, minimizing symptoms of a disease and even curing it in some cases.

Immunotherapies are delivered in a variety of ways. Depending on the particular treatment, it may be given orally—in pill form—or by intravenous (IV) infusion, which may be given multiple times in a hospital setting. Some treatments are injected under the skin like a flu shot.

Some therapies for cancer involve harvesting cells and then engineering them outside the body to better fight the disease. For this, the patient undergoes a chemotherapy preparative regimen to clear their body of lymphocytes, cells that are central to engaging the immune system. Then, those cells are replaced by the more powerful engineered cells in a single IV treatment.

Patients with certain types of cancer may be given immunotherapy alone, while others may be treated with combined immunotherapy and chemotherapy, for instance.

If a person is eligible for treatment with immunotherapy, the type of treatment offered depends on a number of factors, including their condition (not all diseases can be treated with immunotherapy). And the length of treatment varies widely. For cancer, treatment might mean a single dose or multiple treatments given over the course of one or two years. For autoimmune diseases, such as MS, treatment may be long-term, continuing for over a decade for many patients.

Types of immunotherapy include (but are not limited to):

• Immune checkpoint inhibitors: Checkpoints are a natural part of the immune system that keep immune responses from being so strong that they destroy healthy cells. But this can also inhibit the immune response. As the name implies, immune checkpoint inhibitors block those checkpoints so the immune system can more effectively find and attack cancer cells.
• Adoptive cell therapy (or T-cell therapy): This involves removing immune cells called lymphocytes (which are key cancer fighters) from the body so that they can be genetically engineered in a laboratory to enhance their ability to recognize, bind to, and kill cancer cells. The revamped cells are injected back into the body to attack cancer.
• CAR T-cell therapy: This is a promising type of adoptive cell therapy in which lymphocytes are changed to make a protein called chimeric antigen receptor (CAR) that—once injected back into the body—gives these cells the ability to specifically bind to cancer cells that have the target for CAR on their surface. For certain kinds of cell therapy—for example, TIL cells—the lymphocytes are removed from a patient’s cancer and are already capable of recognizing the tumor cells, but they need to be expanded and activated outside the body. More recently, cell therapy with lymphocytes is being used to treat autoimmune diseases by using CAR-T, which can recognize and kill the immune cells in the body that are attacking normal tissues.
• Monoclonal antibodies (mAbs): These are laboratory-made antibodies that mimic those found in the body. (Since monoclonal means “one type,” a treatment would mean multiple copies of one kind of antibody). They work in different ways. For cancer treatment, they are designed to trigger the immune system to attack cancer cells. For autoimmune diseases, they block inflammatory proteins—for example, interleukin-6—to improve inflammation-related symptoms, such as the joint pain and swelling associated with arthritis.

There are several Food and Drug Administration (FDA)-approved immunotherapies to treat certain types of cancers. Some of these are now used as standard treatments for such diseases as bladder, head and neck, esophageal, lung, and renal cell cancer.

But “melanoma is the ‘poster child’ for cancer immunotherapy; it is the disease where it has worked best,” Dr. Sznol says. In fact, the first immunotherapy for cancer was a checkpoint inhibitor for melanoma, which was approved by the FDA in 2011. Part of the reason for its success is that melanoma cells contain many mutations, and the immune system sees those cells as foreign invaders and reacts with stronger and more diverse immune responses. Checkpoint inhibitors unleash these immune responses so they can attack the melanoma cells.

Before immunotherapy became available, just 5% of people with advanced melanoma (melanoma that spreads internally to other organs) survived five years or longer; now, with immunotherapy as a treatment option, that figure is close to 50% or more, Dr. Sznol says. What’s even more remarkable is that many people with melanoma who are given immunotherapy and survive their cancer for at least five years will never relapse or require additional treatment, he adds.

But Dr. Sznol cautions that some cancers respond better to immunotherapy than others. “Even with melanoma, it’s important to remember that only half of the patients will respond to immunotherapies, whereas with some other cancers, it might only be 15% or 20% of patients,” he says.

Many immunotherapy treatments for cancer are still being researched, and patients may have access to those in clinical trials.

As noted above, there are more than 80 distinct autoimmune diseases—and there are immunotherapies for some of the most common ones, including MS, RA, and psoriasis. When the immune system goes awry and attacks the body’s healthy tissues, it causes inflammation and other complications that exacerbate the disease. Immunotherapy drugs lower that activity, targeting the specific components of the immune system contributing to the disease.

The approach is different from some conventional autoimmune disease treatments that suppress general immune function, which makes people vulnerable to disease-causing bacteria and viruses.

Different immunotherapies target different autoimmune conditions. For instance, MS causes lesions on the brain and spinal cord, Dr. Hafler explains. “The immunotherapy drugs don't make you feel better or fix your existing lesions, but they prevent new ones from occurring,” he says.

For type 1 diabetes, an immunotherapy drug called teplizumab (brand name: Tzield®) was approved by the FDA in 2022. It can delay the onset of an advanced stage of type 1 disease in people as young as 8 years old.

“Similar to cancer, it’s important to remember that immunotherapies for autoimmune diseases have varying degrees of efficacy,” Dr. Hafler says. For example, ocrelizumab, a monoclonal antibody, has 98% efficacy against MS, while adalimumab (Humira®), the most common treatment for RA, may be 60% effective or less, he says.

Immunotherapy is often well-tolerated, according to the doctors. As with many drugs, there may be side effects, such as dizziness, fatigue, diarrhea, rash, nausea, joint pain, and weakness. Because immunotherapy can unleash immune reactions that can attack any normal healthy tissue, some patients may develop very severe reactions that affect the colon, kidneys, liver, lungs, heart, endocrine glands, and other internal organs, which require urgent treatment and could even lead to death.

Fortunately, very severe, life-threatening reactions are rare. These can depend on the type of immunotherapy and such factors as a patient’s general health and how advanced the disease is.

For the vast majority of people, most side effects can be reversed, Dr. Sznol says. But if side effects are serious—or if they could become serious—the patient may need a treatment, such as steroids, to “turn off” the immune system. “Generally, treatment with steroids or other immunosuppressants is time-limited; once the side effect resolves, the steroids can be stopped, and the side effects will not recur unless the patient is again treated with a similar type of immunotherapy,” Dr. Sznol says.

For autoimmune diseases, side effects from immunotherapy are usually minimal, Dr. Hafler says, adding that this is a vast improvement over earlier treatments—or, in some cases, no effective treatments at all.

Patients with MS were once treated with a chemotherapy drug called cyclophosphamide, an immune suppression treatment for patients with severe disease, which had such side effects as hair loss and infertility in the short term to an increased risk of leukemia in the long term. “We don't use that anymore,” Dr. Hafler says.

The first step is to consult an appropriate specialist, such as an oncologist or autoimmune disease specialist experienced in the condition you have, the doctors say. “You should ask them, ‘Is immunotherapy a part of my treatment? How is it going to benefit me if I take it?’” Dr. Sznol says.

Not every disease will have an immunotherapy treatment. With cancer, chemotherapy, radiation, and surgery are still key treatment pillars for many patients.

But immunotherapy research is ongoing for a variety of cancers and autoimmune conditions. Scientists are studying how long patients need to be treated with particular immunotherapies, whether they work better when combined with another treatment for particular conditions, and how to determine who will have the best results.

In addition, scientists are studying how to make the treatments more effective for more people with the help of personalized medicine, in which treatments are customized for individual patients based on their genetic profile. “In this endeavor, I think genetic screening will be very useful in helping to get the right drug to the right patient,” Dr. Hafler says.

“The more experts learn, the better equipped they will be to use immunotherapy to treat patients,” Dr. Sznol says.