Isaac Brownell, MD, PhD of the National Cancer Institute, Bethesda, MD provides insight into the possible mechanisms of Merkel cell carcinoma development at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Clinical and pre-clinical evidence shows that Merkel cell carcinoma is highly regulated by the immune system and this may be one of the reasons why Merkel cell carcinoma tends to present late in life. The average age of a person diagnosed with Merkel cell carcinoma is 72 years old, which is 10 years older than the average cancer patient in general. Dr Brownell suggests, it may be that with increased age there is senescence of the immune system, which weakens the immune system and may allow for Merkel cell carcinoma to initiate. Supporting this idea, in immunocompromised populations the rate of Merkel cell carcinoma are much higher. It is suspected that naturally the immune system is involved in supressing this type of cancer and that patients who develop this cancer have either developed a tumor that evades the immune system and then checkpoint inhibitors can intervene to get the immune system back on track. Or another mechanism could implicate the immune axis in the tumor and that’s why checkpoint inhibitors tend to be very effective.