The investigators have shown that hypoxia contributes to tumor cell shedding of MIC through a mechanism involving impaired nitric oxide (NO) signalling. While hypoxia increased MIC shedding in human prostate cancer cells, activation of NO signalling inhibited hypoxia-mediated MIC shedding. Similar to incubation in hypoxia, pharmacological inhibition of endogenous NO signalling increased MIC shedding. These findings suggest that the hypoxic tumor microenvironment contributes to impaired immune surveillance and that activation of NO signalling is of potential use in cancer immunotherapy.