The idea of unleashing the immune system against cancer cells has tantalized doctors, scientists, cancer patients, and their families for decades. Our bodies’ natural defenses are so good at identifying and defeating many intruders (think of the hundreds of germs we encounter each and every day!), yet so sluggish when it comes to attacking cancer cells. That’s because cancer cells are masters of disguise: they trick the body into believing they’ve supposed to be there, so the immune system leaves the cancer cells alone—until now, that is. New immunotherapy treatments are now helping some people with head and neck cancer live longer, healthier lives. Here’s how they work. Immunotherapy allows the immune system to attack and kill cancer cells. Unlike regular cells, cancer cells don’t die normally. They continue to divide, change and spread throughout the body. The immune system doesn’t recognize these dangerous cells as invaders, and cancer cells use all kinds of tricks to stay hidden. These “tricks” keep the immune system at bay. Immunotherapy medication helps the immune system recognize cancer calls as a lethal threat that must be destroyed. How? Tumor genes inside cancer cells often express special proteins that essentially tell the immune system to back off. One type of immunotherapy medication, checkpoint inhibitors, blocks communication between these proteins and immune cells. As a result, the immune system is able to “see” and attack the cancer cells. Checkpoint inhibitors extend survival for some people with head and neck cancer. Until very recently, people with head and neck cancer that progressed despite treatment with chemotherapy had few options. But in 2016, the U.S. Food and Drug Administration (FDA) approved two checkpoint inhibitors for the treatment of head and neck cancer, and progression-free survival is now a reality for some people. Nivolumab (Opdivo) was FDA-approved in April 2016 on the basis of a research study that compared the outcomes of head and neck cancer patients treated with nivolumab or chemotherapy. All patients in the study had head and neck cancer that had gotten worse within six months of undergoing treatment. Historically, the prognosis for such patients is poor; average survival is just six months. The patients who received nivolumab, though, were less likely to die than patients receiving standard treatment. Nivolumab became the first treatment shown to extend life in people with head and neck cancer that progressed after chemotherapy. Pembrolizumab (Keytruda), another checkpoint inhibitor, was FDA-approved to treat recurrent head and neck cancer in August 2016 after research studies showed that it increases both progression-free survival (the period of time that the cancer does not grow) and overall survival in about 20% of patients. Scientists are still learning why checkpoint inhibitors work in some people–and not in others. What researchers don’t yet understand is why checkpoint inhibitors work so well in some people, but not at all in others. Very specific gene mutations within tumor cells likely play a central role. Right now, scientists and doctors can’t predict with certainty which people with head and neck cancer will respond to checkpoint inhibitors and which will not. A lot of research studies are currently underway to try to answer this question. Scientists hope to someday develop a simple blood test that will tell doctors in advance which patients might benefit from treatment with checkpoint inhibitors. The field of immunotherapy is rapidly advancing. Your healthcare provider is your best resource for up-to-date information on head and neck cancer and immunotherapy.