When your immune system identifies something harmful in your body, it makes antibodies to attack and kill it. But with cancer, the process is not so simple.  

For years, doctors have known that the immune system, which includes cells, tissues and organs, mobilizes to find and destroy cancer cells—just as it fights off bacterial or viral infections. 

The difference is that cancer can progress in the patient’s body. This happens, in part, because of the cancer cells’ ability to outsmart specific immune cells called regulatory T cells. Regulatory T cells (a type of white blood cell) are the body’s natural “brake” mechanisms. They prevent their fellow T cells—which kill cancer cells and other foreign invaders—from running rampant and attacking healthy cells and tissue. Cancer cells evade T cells by pretending to be normal, healthy ones. This means that they are essentially under the protection of regulatory T cells.       

So, what if there were a way to help the body’s immune system distinguish cancer cells from healthy ones so it fights off the cancer? That’s the basic idea behind immunotherapy.

In 1999, a milestone in the development of cancer immunotherapies was reached because of research finding by Yale Medicine’s Lieping Chen, MD, PhD, a professor in the Immunobiology department and co-director of the Cancer Immunology Program at Yale Cancer Center. He discovered that a molecule, now called PD-L1, could bind to a certain cell receptor. And in some cases, it could prevent the body’s immune system from attacking tumors. 

Dr. Chen’s research was the foundation for early clinical trials that tested a class of immunotherapy drugs called checkpoint inhibitors designed to prevent that binding action. These drugs have given years of life to patients who responded to it (roughly 20 to 30 percent of late stage cancer patients overall). 

But checkpoint inhibitors are just one type of immunotherapy. Today, different kinds of immunotherapy have been developed and new ones are continually being tested. Immunotherapy is considered to be the future of cancer treatment.   

At Yale Medicine, our team conducts numerous clinical trials that give eligible patients access to the latest immunotherapy drugs. Our researchers and doctors work closely together at the Yale Center for Immuno-Oncology (YCIO) to quickly discover innovative treatment therapies. Yale Cancer Center is one of only 49 National Cancer Institute (NCI)-designated comprehensive centers in the country. Our doctors play a vital role in cancer research, prevention and new treatment approaches.   

On a basic level, immunotherapy works in one of two ways. It can boost mechanisms of the immune system so that it has more strength to fight cancer cells. Or, it can target and destroy certain proteins, or receptors, on cancer cells to prevent them from outsmarting the immune system.

New immunotherapy treatments for cancer are tested all the time. For example, researchers are still in the early stages of investigating vaccines to actively fight cancers. Most take years to become available as standard treatments (to patients not involved in clinical trials). However, several immunotherapy drugs have been approved by the U.S. Food and Drug Administration (FDA) to treat several types of cancer:    

• Targeting monoclonal antibodies. These drugs are chemically produced antibody proteins engineered to attack specific parts of cancer cells. They work in different ways. Some may flag a cancer cell so immune cells can easily find it. Others carry toxins or chemicals that kill cancer cells. These have been approved for more than 10 cancer types, from breast to brain cancers.
• Anti-PD-1/PD-L1 antibody therapy. This is the most established and broadly used type of immunotherapy. Currently, the FDA has approved this therapy for more than 10 cancer types, from non-small cell lung (NSCLC) to breast to advanced melanoma cancers. This drug class gets its name through its mechanism of inhibiting, or preventing, cancer cells from evading the immune system’s T cells. PD-1, a protein found on the surface of T cells, serves as an “on/off” switch to signal T cells whether or not to attack foreign cells. When T cells detect another type of protein, called PD-L1, found on the surface of cancer cells, they receive a signal to leave the cell alone.
• Adoptive cell transfer. This treatment works by increasing the numbers and strength of the body’s naturally occurring immune cells, such as T cells.
  • CAR T-cell therapy: Chimeric antigen receptor (CAR) T-cell therapy has been approved by the FDA for two types of cancers: acute lymphoblastic leukemia (ALL) in children and a form of non-Hodgkin lymphoma called diffuse large B-cell lymphoma. 
  • TIL therapy: Tumor infiltrating lymphocyte (TIL) therapy is still in its early stages and is being tested in melanoma and other cancers. However, no TIL therapy has been approved by the FDA yet.   

When the FDA approves an immunotherapy drug, it does so for a very specific cancer type first—for example, as a treatment for metastatic melanoma, or for kidney cancer that hasn’t responded to a round of chemotherapy. As physicians and researchers conduct more studies on the safety and effectiveness of immunotherapy, its use may be expanded to different cancers. Anti-PD-1/PD-L1 therapy, for example, is now approved for more than 10 types of late stage cancer.

Most immunotherapies are given intravenously, just like IV fluids. Some immunotherapies may be given subcutaneously, or beneath the skin, like a flu shot or an insulin injection.   

Like all cancer treatments, immunotherapy comes with side effects and risks, which can be serious or life-threatening, such as an overreactive immune system. Additional side effects vary widely and include fever, fatigue, nausea, weakness and dizziness.

Yale Medicine is at the forefront of basic and clinical cancer immunotherapy, Dr. Chen says. In addition to the discovery of innovative approaches in the laboratories, Yale Medicine’s doctors are first (or among the first) to conduct various clinical trials using anti-PD-1/PD-L1 cancer immunotherapy for the treatment of melanoma and lung cancer. Yale Medicine is currently one of the largest centers in the country for new clinical trials on lung cancer, melanoma and other types of cancer.