Natural killer cell-based immunotherapy: a new fighter against melanoma?

Changes in the expression of proteins on cancer cell surface are a typical outcome of malignant transformation. Natural killers (NKs) utilize a set of activating and inhibitory receptors that enable them to recognize altered protein expression and then destroy 'stressed' cells such as cancer or virus-infected cells. Major histocompatibility complex class I polypeptide-related sequence A and B (MICA and MICB, respectively) are expressed by various human tumors and can be recognized by activating NK cell receptor NKG2D. However, cancer frequently escapes recognition by NK cells by proteolytic shedding of MICA and MICB proteins. A study carried out by Ferrari de Andrade and colleagues showed that monoclonal antibody targeting the site of proteolytic shedding of MICA and MICB reduced the progression of melanoma in immunocompromised and immune competent mice models by activation of NKG2D. This approach prevented the reduction of essential immunostimulatory ligands (MICA/MICB) and restored NK cell-driven anticancer immunity.

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