Immune activity in Merkel cell carcinoma

Merkel cell carcinoma (MCC) is widely known as a highly malignant skin cancer. The pathogenesis of MCC, however, remains mysterious due to the extremely small number of cases and its prevalence in the elderly. Despite its high-grade malignancy, spontaneous regression occurs with some frequency. The immune activity of the tumor underlies this peculiar behavior. In recent years, immune checkpoint blockade therapies, including the anti-programmed death ligand 1 antibody, have provided successful results. These therapies, however, are ineffective in approximately half the patients with advanced MCC and few treatments are available for those patients. In this review, we summarize the increasing body of evidence relating to the immune activity of MCC and immunological biomarkers. The interesting and sometimes peculiar behavior of MCC, such as their spontaneous regression, is largely due to their high immunosensitivity. Understanding the tumor immunokinetics of MCC should provide critical insight for understanding cancer immunotherapy. Here, we introduce a new classification for MCC according to its immune activity. Combined application of programmed death ligand 1 (a prognostic factor and predictor of the efficacy of immune checkpoint inhibitors in various cancers) with glucose-6-phosphate dehydrogenase (a new promising biomarker for MCC) may enable classification of MCC based on its immune status. Whether the new classification can be used to predict the efficacy of immune checkpoint blockade therapies remains to be evaluated in future studies, but the classification may facilitate future treatment selection.