ISG15 and head and neck squamous cell carcinoma: Consistent with the in vitro finding, multiplex immunofluorescence staining revealed that the ISG15 signal within p-MLKL + necroptotic foci was significantly higher compared to p-MLKL- necrotic foci and non-necroptotic/necrotic cells (Fig. 9A, B), suggesting a high-ISG15 necroptotic microenvironment in HNSCC.