In a new study published in The Journal of Clinical Investigation, a team of scientists used sample cells from Merkel cell carcinoma (MCC) patients to study ways to boost the immune system's response to this rare but aggressive form of skin cancer commonly caused by exposure to ultraviolet (UV) radiation from the sun.Melanoma, a much more well-known form of skin cancer that is highly treatable, especially when caught early. It starts in the pigment-producing cells of the skin called melanocytes, and it often appears as a new or changing mole. Because of the prevalence of melanoma, many people assume that skin cancer is relatively easy to treat, and is therefore, not much of a concern. However, melanoma in itself can be dangerous, all skin cancers are not created equal.MCC usually starts as a firm bump on the skin that is either red or purple in color. These bumps tend to show up in areas exposed to the sun’s rays, such as the face, neck, arms, and legs. The growth can expand very fast and it’s important for patients to seek medical attention immediately.The team, led by Professor Sine Reker Hadrup from DTU, included experts from universities and hospitals in the United States, Germany, and Denmark. An innovative approach was used to identify specific elements (called epitopes) in the Merkel cell polyomavirus (MCPyV) that can be recognized by the immune system’s T cells and have been directly linked to MCC. Healthy immune systems are normally able to fend off these epitopes, but those who have compromised immune systems, such as the elderly or those with autoimmune disorders, are more susceptible to the disease.

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The team extracted T cells and exposed them to a nanostructure devised to stimulate an immune response against the MCPyV. This method, based on a DTU-patented technology, allowed a large numbers of T cells to be created capable of targeting and killing cancer cells. Ultimately, it was able to identify and fight cancer cells in samples from 9 out of 10 patients.Professor Hadrup discussed importance of the findings, stating, "In the trial, we show that the expansion strategy for immune cells that can fight Merkel cell cancer is relevant for people with this type of cancer. We have designed some molecular structures that contain a number of different molecules that can activate the reaction in the immune system that can defeat the cancer cells."The next step would be to conduct larger studies and eventually use the results in clinical trials with Merkel patients in order to develop a new type of immunotherapy, offering hope to patients despite the cancer’s poor prognosis.Merkel predominantly affects individuals over 70 and is slightly more common in women than man. Usually by the time it’s diagnosed, about one-third of cases have already metastasized, meaning it’s spread from its initial location to other areas of the body. Early detection and effective treatment are key to survival. Standard treatments include surgery, radiation, immunotherapy, and chemotherapy, but survival rates with these current methods are low.The team concluded in its paper, “Understanding the immune response to MCC during ICI therapy is important for our understanding of immunologic events underlying blockade of the PD-1 pathway. This knowledge can be used as a predictive biomarker for patient stratification where a blood-based source would be highly favorable, since it is minimally invasive and easily accessible compared with a tumor biopsy. Moreover, expanding our knowledge related to T-Ag–derived epitopes of relevance for T cell recognition and tumor cell killing is critical for the development of new immunoprecision therapeutic strategies targeting such Ags.”

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T antigen-specific CD8+ T cells associate with PD-1 blockade response in virus-positive Merkel cell carcinomaResearch paves way for new forms of immunotherapy to treat people with Merkel cell cancer