Immunosuppressants: What is their role in cancer care?

An immunosuppressant is anything that diminishes the body’s natural ability to respond to threats, such as cancer or viruses, like the ones that cause the common cold.

Sometimes, due to autoimmune disorders such as lupus, multiple sclerosis, rheumatoid arthritis, scleroderma or Sjögren’s syndrome, the immune system is already suppressed. But in the context of cancer care, immunosuppressants are drugs that we sometimes give to patients. 

So, why might you need an immunosuppressant? How do immunosuppressants work? And, how are they used in the treatment of cancer and its side effects?

Read on for the answers to these questions and more. 

Why might somebody need an immunosuppressant?

We use immunosuppressants during cancer treatment for several reasons. 

Before a stem cell transplant

We give patients chemotherapy before a stem cell transplant to kill any remaining cancer cells and to dampen their immune systems. The goal is to create a “clean slate.” That way, when donor cells arrive, they don’t have a big fight on their hands. It’s not impossible for donor cells to engraft properly if the host’s own stem cells are still present, but it does make the process much more difficult. 

After a stem cell transplant

We use various drugs after a stem cell transplant to prevent: 

• The patient’s own immune system from rejecting the donor’s cells
• The donor’s cells from attacking the patient’s tissues, a condition known as graft vs. host disease (GVHD)  

Other situations

Inflammation can be a positive sign that your immune system is working correctly. But when inflammation gets out of control, it can start causing problems. So, the “fire” must stay within certain boundaries. You just want the warmth and the heat and the glow of a “controlled burn,” not a raging wildfire. So, sometimes, we use steroids or other drugs to calm things down when a patient’s immune system gets too ramped up.

Immunosuppressants are also used quite a bit in solid organ transplants, but we don’t perform those here at UT MD Anderson. 

How do immunosuppressants work?

That depends. The immune system is quite complex, so there are many different ways to calm it down. The two main branches involved are: 

1. Cell-mediated immunity, which is driven by T cells
2. Humoral immunity, which is driven by antibodies and B cells   

Steroids eliminate both B cells and T cells, so they cover it all. Chemotherapy does the same thing. Other drugs target just one type of cell. So, it really depends on which branch of the immune system you’re looking to calm down. 

What are some examples of immunosuppressants?

Name: Tacrolimus  
Class: Macrolide lactone  
How it’s used: A calcurine inhibitor that reduces the activation of T cells and the production of a signaling protein called IL-2 
How it’s administered: comes in pill and IV form 

Name: Sirolimus  
Class: Macrolide antibiotic 
How it’s used: an mTOR inhibitor that blocks the activation of T cells 
How it’s administered: comes in pill and liquid form 

Name: Mycophenolate  
Class: Antimetabolites 
How it’s used: mimics the nutrients T cells need and disrupts their growth process, which causes the cells to wear out and die much sooner than they normally would 
How it’s administered: comes in pill and IV form 

Name: Abatacept  
Class: Biologics 
How it’s used: blocks the initial activation of T cells 
How it’s administered: comes in IV form only

Name: Cyclophosphamide 
Class: Alkylating agent 
How it’s used: given on days 3 and 4 after a stem cell transplant to reduce the reactive T cells that can drive GVHD  
How it’s administered: comes in IV form only 

But these are all different classes of drugs. The one thing they have in common is that they can block or calm down T cell activation, the process of “waking up” the immune system to attack.  

Which immunosuppressant is used the most?

Tacrolimus is probably the one we use most frequently with our stem cell transplant patients. 

How long do you have to remain on immunosuppressants?

That depends. If you’ve had a kidney, liver or lung transplant, you’ll likely be on them for the rest of your life. The reason is that those organs will continue to express their original donor’s proteins, which your body would otherwise still recognize as “not self” and attack, resulting in organ rejection. But stem cell transplant patients don’t normally have to be on immunosuppressants for very long.

Stem cells can develop into many different types of cells. Once they’ve engrafted properly and started copying themselves, all the new T cells and B cells created by your bone marrow will become your new immune system and become tolerant of your body tissues. That means any proteins expressed by your tissues will be familiar to your new immune cells.

That being said, most stem cell transplant recipients can expect to be on immunosuppressant therapy for about six months. If we see no evidence of GVHD during the first 100 days after a transplant, we can talk about stopping earlier. In some cases, that could be as soon as four months after a transplant. 

Can anything else cause immunosuppression?

Yes. Autoimmune disorders. But I tend to think of those as a supply and demand problem. 

There’s only a limited supply of T cells and B cells in the body. With autoimmune disorders, the body is too busy attacking its own tissues to fight off infections. Its treatment is often geared toward eliminating T cells and B cells. So, that can reduce your immune response even more.

Viral infections can also suppress the immune system, especially if they infiltrate the bone marrow and affect the new graft in stem cell transplant recipients.

Jeremy Ramdial, M.D., is a stem cell transplant specialist.

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