Tumor-exclusive peptides from shared and individual antigens in the HLA-ligandome of oropharyngeal squamous cell carcinoma

Introduction Cancer-antigens are presented to the immune system via Human leucocyte antigens (HLA). The HLA-ligandome in oropharyngeal squamous cell carcinoma (OPSCC) has not been described previously.

Material and Methods OPSCC tumor biopsies from 40 patients and tonsillar tissue from 5 healthy donors were analyzed. HLA molecules were extracted from fresh frozen OPSCC biopsies, HLA ligands were isolated by high performance liquid chromatography (HPLC) and analyzed by tandem mass spectrometry (MS/MS). Tumor-exclusive peptides (TEP) were identified by comparative profiling against normal tonsil tissue and an in-house benign and malignant HLA-ligandome database. Whole exome sequencing of RNA and DNA was also performed.

Results OPSCC were classified as HPV+ (n=22) or HPV- (n=18) based on RNA-seq data. In total, 25228 HLA class I presented peptides from 9485 source proteins and 15203 HLA class II presented peptides from 4634 source proteins were detected. Peptides derived from the cancer-testis antigens IMP3, KDM5B, CTNNA2 and ATAD2 were found in = 30 %  of patients. In total, 3746 HLA class I TEP and 5096 HLA class II TEP were identified. Some TEP were only found in HPV+ or HPV-, whereas others were shared among both, HPV+ and HPV-.

Conclusion The HLA-ligandome of OPSCC contains both shared and individual TEP and differs by HPV-status. Based on these results, semi-personalized or personalized cancer vaccines could be developed.

Poster-PDF A-1495.pdf

DFG (GRK-2254), Universität Ulm (Clinician Scientist Programme)