New avenues for melanoma immunotherapy: Natural Killer cells?

Human solid malignant tumours may be particularly resistant to conventional therapies. Among solid tumours, immunological features of cutaneous melanoma have been well characterized in the past and today melanoma patients are routinely treated with the anti-immune checkpoints immunotherapy that has completely changed metastatic melanoma treatment and prognosis. Two cytotoxic cell populations may lead to the physical elimination of tumour cell targets: cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Tumour recognition by CTLs depends on major histocompatibility complex (MHC) class I molecules, while NK cells recognize tumours expressing low or null levels of MHC class I molecules. Despite this well-established complementarity, NK cells are still left behind in the optimization of innovative immunotherapy approaches. NK cells are members of innate lymphoid cells (ILCs) that play a critical role in early host defence against invading pathogens and transformed cells. Recent findings suggest that NK cell frequencies directly correlate with the overall survival of ipilimumab-treated melanoma patients. Furthermore, in vitro and in vivo evidences indicate that NK cells can selectively kill cancer stem cells, reducing tumour size and delaying metastatic progression. The aim of this review is to provide a survey of the evidences indicating NK cells as an excellent candidate to complement the newest solid tumour immunotherapy approaches.