Exploiting natural killer cells for therapy of melanoma

During the recent years, immunotherapy has obtained substantial impact on the clinical treatment of melanoma. Besides promising approaches based on T lymphocytes, natural killer (NK) cells have gained more and more attention as anti-melanoma effector cells. NK cell activation is inhibited by HLA class I molecules expressed by target cells, so they preferentially attack tumor cells that express low levels of HLA class I. Partial or complete loss of HLA class I expression is a frequent event during the development of melanoma. In parallel, ligands for activating NK cell receptors become induced upon malignant transformation. Thus, melanoma cells are often efficiently recognized and lysed by NK cells at least in vitro. In vivo, however, melanomas have developed multiple sophisticated strategies to escape from NK cell mediated attack. Several novel approaches aim at harnessing NK cells to treat melanoma patients and to counteract existing tumor escape mechanisms. This review summarizes the most recent advances in the field.