Natural killer cell recognition of melanoma: new clues for a more effective immunotherapy

Natural killer (NK) cells participate in the early immune response against melanoma and also contribute to the development of an adequate adaptive immune response by their crosstalk with dendritic cells and cytokine secretion. Melanoma resistance to conventional therapies together with its high immunogenicity justifies the development of novel therapies aimed to stimulate effective immune responses against melanoma. However, melanoma cells frequently escape to CD8 T cell recognition by the down-regulation of major histocompatibility complex (MHC) class I molecules. In this scenario, NK cells emerge as potential candidates for melanoma immunotherapy due to their capacity to recognize and destroy melanoma cells expressing low levels of MHC class I molecules. In addition, the possibility to combine immune checkpoint blockade with other NK cell potentiating strategies (e.g., cytokine induction of activating receptors) has opened new perspectives in the potential use of adoptive NK cell-based immunotherapy in melanoma.• Ministerio de Ecomomía y Competitividad. Ayudas SAF2009-09711 y SAF2013-46161-R, para Raquel Tarazona Lafarga • Ministerio de Salud. Ayudas PS09/00723 y PI13/02691, para Rafael Solana Lara • Junta de Andalucía. CTS 208, para Rafael Solana Lara • Junta de Extremadura y Universidad de Extremadura cofinanciadas Fondo FEDER. Ayudas para el Grupo de Investigación INPATT: GRU10104 y GR15183, para Raquel Tarazona Lafarga y Esther Durán Flórez • Ministerio de Economía y Competitividad y Fondos FEDER. Contratos QLRT-2001-00668 “Outcome and Impact of Specific Treatment in European Research on Melanoma, OISTER” y Proyecto LABPOLEpeerReviewe