Dr. Michael Postow explains how immunotherapy works and who it can help.
Immunotherapy is one of the most promising approaches to cancer treatment. Unlike other forms of cancer treatment, in which drugs or radiation target cancer cells directly, immunotherapy targets your immune system, boosting its innate power to fight the cancer.
But how does it work and who can it help?
We asked melanoma oncologist Michael Postow, MD, an expert in immunotherapy at Memorial Sloan Kettering Cancer Center (MSK), to address the most frequently asked questions.
1. How is the immune system able to fight cancer on its own?
Your immune system keeps you safe from many threats — not only infectious ones like bacteria and viruses, but also cancer. It does this by recognizing and attacking things that appear foreign or dangerous. Because cancer cells are genetically mutated, they look different to your immune system than healthy cells. Your immune system is constantly ridding your body of mutated cells that could lead to cancer.
2. How do cancer cells evade the immune system?
Occasionally, cancer cells trick the immune system into sparing them from attack. One way is to step on an immune cell’s brakes, which keep immune cells from attacking healthy cells. Cancer cells can also alter the tumor microenvironment in surrounding tissue to make it hostile to immune cells.
3. What are the types of immunotherapy?
There are three main types of immunotherapy:
- Immune checkpoint inhibitors: These are drugs that release the brakes on immune cells, allowing them to go after cancer cells.
- Adoptive cell-based therapies: Sometimes called living drugs, these are natural or engineered versions of a person’s own immune cells that are multiplied in the lab and given back to the person in large numbers. These therapies include CAR T and TIL. Having more of these cells in the body is like having a bigger army to naturally fight cancer.
- Cancer vaccines: These are designed to either prevent or treat cancer, by training the immune system to identify dangerous cells that have telltale markers, called antigens. Recently, an MSK clinical trial showed that a personalized cancer vaccine may activate the immune system in patients with pancreatic cancer. But more research is needed.
4. Which cancers can be treated with immunotherapy?
Immunotherapy works well for cancers that have distinguishable markers that our immune system is able to recognize. There are several broad categories:
- Cancers with many genetic mutations: These are easier for the immune system to detect because they look so different from normal cells. Some cancers, like melanoma and lung cancer, can develop many mutations from the genetic damage caused by sunlight and cigarette smoking, respectively. Other cancers, including certain types of colon cancer, may develop many mutations as a result of an underlying genetic condition.
- Cancers with high levels of PD-L1 expression: PD-L1 is a protein that some cancers make that can step on an immune cell’s brakes and cause the immune response to shut down. Certain cancers with high amounts of this protein are considered good candidates for anti-PD-1 immunotherapy drugs such as pembrolizumab and nivolumab.
- Cancers with distinctive markers on their surface: Certain blood cancers have markers on their surface that make them good targets for CAR T immunotherapy. The surface marker CD19 on B cell leukemias is a good example.
5. What are the side effects of immunotherapy?
The most common side effects result from the immune system overreacting to normal tissues in the body. They include skin problems like rash or itching, chills and other flu-like symptoms, gastrointestinal issues like diarrhea, and pain from joint inflammation. These side effects can be very dangerous if they involve vital organs, such as the lungs, and go untreated. MSK doctors are experts in caring for people with immune-related adverse events.
6. What percentage of cancer patients can immunotherapy help?
It varies by cancer type but, on average, immunotherapy helps:
- Between 15% and 30% of patients who have common solid tumors such as lung, bladder, and kidney cancer.
- Between 45% and 60% of patients with certain skin cancers, as well as people with solid tumors that have a type of mutation called MMRd/MSI-high.
7. Why does immunotherapy stop working in some patients?
Immunotherapies may stop working when cancer cells evolve to evade immune cells, often by losing the specific marker or markers that the immune cells were using to identify it. This is called antigen escape or immune escape. Cancer and the immune system are in a constant battle to see which can get the upper hand; immunotherapy intends to strengthen the immune response to ensure it continues to control cancer as long as possible.
8. Is there anything patients can do to boost their own immune system so immunotherapy works better?
There are no specific actions a person can take to ensure their immunotherapy is successful. However, some research indicates patients do better when they maintain a healthy gut microbiome by eating a diet high in plant fiber, avoiding unnecessary antibiotics, and avoiding probiotics.