to treat adults and children above 12 years with metastatic MCC. In December 2018, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co. Inc.) for all ages (adults and pediatrics) with recurrent locally advanced or metastatic Merkel cell carcinoma Nivolumab (brand name Opdivo, Bristol-Myers Squibb) is in phase III/IV clinical trials Ipilimumab (brand name Yervoy, Bristol-Myers Squibb) is in phase II clinical trials for use in adults with metastatic MCC. Studies to date have shown a clinical response rate between 50 and 65% for MCC treated with PD-1 pathway inhibitors. Suggestions for further immunotherapy research areas have included therapeutic vaccines or epigenetic modification of HLA-receptors. Prognosis According to the American Joint Committee on Cancer (AJCC), the natural course of MCC is "variable and depends heavily on the stage at diagnosis". Staging of MCC is classified according to the TNM staging system, a notation system that describes the stage of cancer according to the size of the primary tumor (T), the degree of spread to regional lymph nodes (N), and the presence of distant metastasis (M). A combination of T, N, and M stages dictate the final clinical stage group (0, I, IIA, IIB, IIIA, IIIB, IV). Advanced stage (i.e. increased size of the tumor, spreading of the tumor into surrounding and/or distant tissue, and involvement of lymph nodes) is associated with lower survival rates. The National Cancer Data Base has survival rates collected from nearly 3000 MCC patients from year 1996–2000 with 5-year survival rates listed as follows: Stage IA: 80%. Stage IB: 60%. Stage IIA: 60%. Stage IIB: 50%. Stage IIC: 50%. Stage IIIA: 45%. Stage IIIB: 25%. Stage IV: 20%. 5 yr survival may be 51% among people with localized disease, 35% for those with nodal disease, and 14% with metastases to a distant site. Several other features may also affect prognosis, independent of tumor stage. They include MCV viral status, histological features, and immune status. In viral status, MCV large tumor antigen (LT antigen) and retinoblastoma protein (RB protein) expression correlates with more favorable prognosis, while p63 expression correlates with a poorer prognosis. Histological features such as intratumoral CD8+ T lymphocyte infiltration may be associated with a favorable prognosis, while lymphovascular infiltrative pattern may be associated with a poorer prognosis. Immune status, especially T cell immunosuppression (e.g., organ transplant, HIV infection, certain malignancy) predicts poorer prognosis and higher mortality. The antibody