Reviewed and edited by: Danielle Leonardo, M.D. Medical Oncologist

Your immune system has the power to fight diseases, even aggressive cancers like mesothelioma. But the immune system needs help sometimes. When doctors do things to help your immune system fight better against diseases, it’s called immunotherapy.

Several types of immunotherapy treatments have had some success against mesothelioma. One of these treatments is PD-1 inhibitor drugs. You may not know what PD-1 is and what it does in your body, so let’s take a look.

What is PD-1?

One of the strongest weapons your immune system has is T-cells. T-cells can destroy the cells of mesothelioma tumors. But the T-cells need to be turned on. If they’re off, they can’t do anything.

A T-cell has little structures on its surface called PD-1. PD-1 is an on/off switch for the T-cell. The way PD-1 works is that it’s a receptor, so it receives things. There are certain proteins PD-1 likes to receive and attach to, especially a protein called PD-L1.

When PD-1 receptors aren’t attached to anything, the T-cells are on and they fight mesothelioma tumor cells. But when PD-L1 proteins are around, they stick to the PD-1 receptors on T-cells. This turns off the T-cells, meaning they can’t fight the mesothelioma tumors.

Here’s the bad news: Cancer cells are able to make PD-L1. They pump out this PD-L1 protein that sticks to PD-1 receptors. That means T-cells get turned off, making it easier for cancer tumors to grow.

The solution? Find a way to block the PD-1 receptors from attaching to PD-L1. Then the T-cells would stay on instead of being turned off, so they could keep destroying tumor cells.

The way to do this is with PD-1 inhibitors.

What do PD-1 inhibitors do against mesothelioma?

PD-1 inhibitors are a type of drug for mesothelioma and other cancers. Some examples are pembrolizumab and nivolumab.

PD-1 inhibitors block PD-1 from attaching to PD-L1. These drugs create a cap that covers PD-1 receptors so PD-L1 can’t stick to the PD-1 receptors. With PD-L1 not getting in the way, T-cells can stay turned on and keep fighting mesothelioma tumors.

How well do PD-1 inhibitors work?

Studies have been done to find out how well PD-1 inhibitors work against mesothelioma. The results so far have been mixed. When people with mesothelioma were given PD-1 inhibitors, about 20-30% of them had reduced tumors.

PD-1 inhibitors can also have side effects. The most common side effects are:

  1. Fatigue
  2. Skin rash, itching, changes in skin color
  3. Diarrhea, nausea, vomiting, loss of appetite
  4. Cough, shortness of breath, difficulty breathing
  5. Hormonal imbalances, thyroid problems
  6. Elevated liver enzymes, liver inflammation

These side effects aren’t the same for everyone. Different people have different side effects, and some have more side effects than others.

Why are PD-1 inhibitors such a hit-or-miss? Why does this treatment work for some people and not others, and why are the side effects different in different people?

Scientists are doing research now to figure out these answers. They’re trying to find ways to predict who’s most likely to benefit from PD-1 inhibitors. It depends on each person’s overall health, their immune system health, and the characteristics of their tumor.

PD-1 inhibitors keep T-cells from being turned off. When T-cells are on, they can fight mesothelioma. That’s why PD-1 inhibitors can be good for mesothelioma patients. This treatment doesn’t work for everyone, and there may be side effects. But scientists are making progress to find out how to make it work for as many people as possible.