TNFSF10 and squamous cell carcinoma: The function of many proteins involved in death receptor signalling and apoptosis induction is regulated by ubiquitination and subsequent proteasomal degradation.39 In various other TRAIL-resistant cancer cells, including cell lines derived from squamous cell carcinomas, inhibition of proteasomal activity resulted in enhanced sensitivity to TRAIL-induced cell death.22,23 Here we show that combination treatment with recombinant TRAIL and low doses of the clinically approved proteasome inhibitor bortezomib displays synergistic cytotoxicity in all HPV+ HNSCC cell lines tested.