Montefiore in the News
How It Works: Immunotherapy for Advanced Lung Cancer
- April 8, 2021
Lung cancer is one of the most common forms of cancer and is the leading cause of cancer deaths worldwide. Immunotherapy uses the body’s immune system to attack and kill cancerous cells.
How does immunotherapy work?
The immune system works by recognizing foreign substances in the body and destroying them. Cancer is a foreign substance in the body that the immune system should ideally identify and destroy.
However, cancer cells have found ways to evade immune system detection. One way they do this is by expressing certain proteins, known as checkpoint proteins, on their surface.
The immune system typically uses these proteins as markers to prevent it from attacking healthy cells in the body. However, cancer cells avoid detection because they express these checkpoint proteins and trick the immune system into thinking they are healthy cells.
Typically, immunotherapy disables these checkpoint proteins on the surface of the cancer cells. This causes the immune system to recognize the cancerous cells as foreign substances and mount an attack against them.
“The general way [immunotherapy] works is the same with all cancers, but lung cancer does seem to be one of the types of cancers that benefit most from immunotherapy,”
Dr. Sarah Goldberg, associate professor of medicine (medical oncology) at Yale Cancer Center, CT, explained. “These immunotherapies can work extremely well in some people with lung cancer, while others do not benefit as much. At this point, it’s not entirely clear why,” Dr. Goldberg added.
Types of immunotherapy for lung cancer
Several different types of immunotherapies available can treat individuals with lung cancer.
Immune checkpoint inhibitors
Immune checkpoint inhibitors are the primary category of immunotherapy drugs that doctors use to treat people with lung cancer. They are drugs that target and block specific immune checkpoint proteins, boosting the immune system’s response to cancer cells.
There are two classes of immune checkpoint inhibitors for lung cancer: PD-1/PD-L1 inhibitors and CTLA-4 inhibitors.
“Most of the immunotherapies approved for the management of lung cancer belong to the same family — PD-1/PD-L1 inhibitors,” Dr. Balazs Halmos, director of the Multidisciplinary Thoracic Oncology Program at Montefiore Health System and professor of medicine at Albert Einstein College of Medicine, clarified. “Another class of agents also approved but less frequently used are called CTLA-4 inhibitors. “
PD-L1 is a checkpoint protein typically found on healthy cells. PD-1 is a receptor found on a type of immune cell called a T cell.
PD-1/PD-L1 inhibitors help keep T cells from attacking healthy cells in the body. When the protein PD-L1 attaches to the receptor PD-1, it sends signals to the T cells to leave the healthy cells alone.
However, cancer cells sometimes produce PD-L1 proteins. When this occurs, the cancer cells send “off” signals to the immune system, preventing it from attacking the cancer cells.
However, the interaction of the PD-1/PD-L1 checkpoint inhibitors disables this rogue PD-L1 protein on the cell. As a result, the receptors on the T cells do not attach to them or receive a message saying they are healthy cells. This means that the T cells identify the cancer cells as an enemy and kill them.
Sometimes, doctors can test the cancer cells to see if they carry the PD-L1 markers. This helps them predict how likely they are to respond to the PD-1/PD-L1 inhibitors.
The Food and Drug Administration (FDA) has approved the following PD-1 inhibitors:
- nivolumab (Opdivo)
- pembrolizumab (Keytruda)
- cemiplimab (Libtayo)
Currently, the only two only FDA-approved PD-L1 inhibitors are atezolizumab (Tecentriq) and durvalumab (Imfinzi).
These checkpoint inhibitors target a checkpoint protein called CTLA-4 on T cells. CTL-4 inhibitors block the protein and stop it from working. Consequently, the body releases extra T cells to attack the cancer cells.
The only FDA-approved CTLA-4 drug is ipilimumab (Yervoy).
“This is a very different class of agents, basically instigating “lazy” T cells to get more active and move out of their “homes” (the lymph nodes) into the cancer microenvironment, where they are needed,” Dr. Halmos said.
“In certain types of cancer, it seems that a combination of the two types of checkpoint inhibitors can work better than just one,” Dr. Halmos continued. “Such a combination is also approved for the management of advanced PD-L1-positive lung cancers. The same combination along with chemotherapy is also approved for all types of lung cancers, including PD-L1 negative advanced lung cancers.”
A doctor typically administers checkpoint inhibitors intravenously.
Other immunotherapies under investigation for lung cancer
In addition to immunotherapies, researchers are also investigating other treatments.
Adoptive cell therapy
Adoptive cell therapies aim to encourage the immune system to fight cancer cells. However, they do so in different ways than checkpoint inhibitors.
Two kinds of adoptive cell therapies currently under investigation are tumor-infiltrating lymphocyte (TIL) therapy and chimeric antigen receptor (CAR) T cell therapies.
“The general idea is trying to take immune cells from a patient, and either grow them outside of the body or alter them in such a way that they can be injected back into the patient and fight the cancer cells,” Dr. Goldberg, who is also research director at the Center for Thoracic Cancers, Smilow Cancer Hospital, CT, said.
“It’s a huge area of investigation right now, especially the CAR T cell therapies, as those have already demonstrated some effectiveness in people with certain kinds of lymphomas and leukemias,” Dr. Goldberg added. “Many of us are hopeful that this may be the future of immunotherapy. But so far, there’s no proof that they are effective overall in people with lung cancer.”
Cancer vaccines are another area of investigation.
Vaccines are substances that a healthcare professional injects into a person’s body to kick off an immune response against certain infections. While doctors traditionally use vaccines to prevent diseases in healthy people, ongoing research is investigating whether and how they can treat illnesses and diseases.
“This has been a big area of investigation for decades. Some have been tested, but we have not yet seen a vaccine that is successful in people with lung cancer,” Dr. Goldberg explained. “That’s not to say there’s no hope for a vaccine treatment in the future — it’s still being studied. It might be that it needs to be combined with another immunotherapy, or it may be a case of just finding the right vaccine.”
Immunotherapy is one of several types of treatments for lung cancer. The treatment uses a person’s immune system to fight and destroy cancer cells. Unlike chemotherapy, it does not affect healthy cells, too.
A person can talk with a doctor about their treatment options to see if immunotherapy is right for them. There are also many treatments under investigation that may become available in the future.
Last medically reviewed on April 8, 2021