The HLA-ligandome of oropharyngeal squamous cell carcinomas reveals shared tumor-exclusive peptides for semi-personalized vaccination

Oropharyngeal squamous cell carcinoma (OPSCC) is diagnosed in 93,000 patients worldwide per year and 51,000 annual deaths can be attributed to this disease. OPSCCs are either human papillomavirus associated (HPV-positive) cancers or non-virally induced, primarily tobacco and alcohol associated (HPV-negative) cancers. MS analysis enabled the identification of naturally HLA-presented peptides in OPSCC tumor tissue. By comparative profiling against benign HLA ligandomic datasets, we demonstrated that tumor-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi-) personalized strategies.