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Immunotherapy is one of the most exciting new approaches for treating several types of cancer, including lung cancer. Immunotherapies work by boosting your body’s own natural defenses to fight cancer. Several immunotherapies are currently being developed and tested in clinical trials for a variety of lung cancer types and stages. At the time this was published, the FDA has approved three immunotherapy drugs for the treatment of metastatic non-small cell lung cancer if chemotherapy is no longer working: nivolumab (Opdivo®), pembrolizumab (Keytruda®) and Atezolizumab (Tecentriq®). These drugs are given through the veins (intravenously or through an IV). Other similar drugs are under development and are likely to be approved soon. Keep in mind that these treatments for lung cancer are still new, therefore more research must be done to understand which people are most likely to benefit and how best to use the treatments. Ask your doctor if there are any available immunotherapy treatments or clinical trials that might be right for you. 

What is the Immune System and How Does It Work?

Your immune system is a network of specialized cells, tissues, and organs working together to defend your body from foreign invaders. It does this through its ability to recognize things that do not belong in the body, such as bacteria, viruses, or cancer cells. The frontline of the immune system includes cells circulating in your bloodstream — known as white blood cells. There are a number of different types of white blood cells, all of which attack foreign substances in different ways. Lymphocytes are one of the main cell types of the immune system, and they are particularly important in fighting cancer. One type of lymphocyte, called T-lymphocytes or T-cells, have specialized structures on their surface that can recognize when a cell is infected or is a cancer cell. When this happens, the T-cell starts a process leading to the destruction of the infected or cancerous cell. 

Your Immune System: What's Supposed to Happen


What Sometimes Happens

How Does Immunotherapy Work?

Because the immune system can be so powerful, the body has control mechanisms in place to prevent it from accidentally attacking normal, healthy tissues, such as the joints, bowels, or skin. One way this happens is through proteins found on the cells of the body called “checkpoint proteins.” PD-1 is a type of checkpoint protein that is found on T-cells and helps to regulate the immune response. Under normal circumstances, PD-1 binds to another protein called PD-L1, which helps “turn off” the T-cells so that they don’t attack normal body organs and tissues.

In some cases, cancer cells can find ways to use these control mechanisms to trick the immune system into thinking that they are “normal” and should not be attacked. One way they do this is by producing their own PD-L1. If a cancer cell produces this protein and that PD-L1 binds to PD-1 (Figure 2), the T-cell no longer recognizes the cancer cell as something foreign. The T-cell becomes inactivated and will no longer attack, making the cancer cells “invisible” to the patrolling T-cells, allowing them to escape. This allows cancer cells to continue to grow and spread.

Researchers have developed several strategies for strengthening the immune system against tumors. One such strategy is to prevent cancer cells from making themselves “invisible.” Drugs that use this strategy are sometimes called “checkpoint inhibitors.”

Nivolumab and pembrolizumab work by binding to the PD-1 on T-cells so that they are no longer available to bind with PD-L1 (Figure 3A). That reduces the cancer cell’s ability to trick the immune system. Atezolizumab works by binding to PD-L1 instead of to PD-1 (Figure 3B), but the result is the same: PD-L1 and PD-1 can no longer bind to each other, allowing the T-cells to recognize the tumor cells and destroy them. Your doctor may recommend testing your tumor for PD-L1 before prescribing one of these treatments. Some studies suggest that this test may help your doctor determine if immunotherapy is right for you.

It is important to know that immunotherapies work differently from chemotherapy. When a patient receives chemotherapy, changes in the size of a tumor can be measured quickly, often within days. With immunotherapy, the benefits can take much longer to recognize. Researchers aren’t sure exactly why this happens, but it may be because the immune response takes a little while to become fully active. In some patients, immunotherapy causes T-cells and other immune cells to flock to the tumor, making it appear to actually get larger before it begins to shrink. Your doctor will work with you to determine how to best monitor your progress while you are on an immunotherapy. 

With Immunotherapy, the Good Guys Win!

What Side Effects Can Occur With Immunotherapy?

Because immunotherapies work by enhancing or turning on the immune system, they can sometimes cause your immune system to become overactive and attack normal tissues or organs.

This can be a particular concern in patients who have had an organ transplant or who already have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus. You should discuss with your doctor if you have experienced any of these before starting an immunotherapy. The most common side effects patients experience with immunotherapies are mild and can include fatigue, itching, skin rashes, muscle, joint or bone pain, and nausea. In rare cases, the immune system over-reacts, which can cause more serious side effects if they result in your body’s own defenses attacking normal organs. This is most commonly seen in the lungs, liver, intestines, kidney or hormone glands. When this happens, conditions such as pneumonitis, a lung problem with symptoms of cough, chest pain, or shortness of breath, or colitis, an intestinal problem that can result in diarrhea or tears or holes in the intestine, can occur. Be sure you talk to your doctor about any concerns or side effects you experience during your treatment.



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This information is not designed to be a substitute for medical advice provided by your treatment team.
Last updated 10/2016

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