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

Abstract

Background The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies. Methods Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens. Results MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse. Conclusion Tumour-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)personalised strategies.

Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies

“…As we were interested in the applicability of the HLA score, we first analyzed frequencies of particular HLA traits. Here, we confirm an enrichment in B51 carriers compared to healthy blood donors recently reported ( 35 ). However, compared to the training cohort and independent validation cohort of our earlier investigation ( 11 , 12 ), HLA-C homozygosity was the only HLA trait demonstrating a lower frequency in HPV-driven HNSCC (20.2% versus 30.3%; p = 0.093), whereas all other frequencies of particular HLA traits were not different (all p > 0.22).…”

“…The other HLA antigens included in the model are DR15 and DQB1 homozygosity besides A11 and two CREGs ( 32 – 34 ), A1C and B12C. DR15 was described as a risk factor for cervix carcinoma in numerous investigations and also detected in HPV-related OPSCC ( 35 ), and according to the strong linkage disequilibrium of DR15 and DQ6 (haplotype DR15-DQ6 according to HLA-DRB1*15-DQB1*06), DQB1*06 that is an independent predictor for PFS in HNSCC may have missed inclusion in the new model due to inclusion of DR15 that achieved a higher level of significance and therefore was data-dependent and automatically extracted to be included in the model, which is the recommended approach ( 29 – 31 ). However, DQB1 homozygosity independently reduces PFS.…”

“…Besides the implication of A3 in the reduced ability to eradicate tumors in response to immune-checkpoint blockade ( 36 ), B18 may essentially contribute to impaired response to neoantigens including HPV-derived peptides. B18 is known to be the HLA-B member with the lowest binding capability among members of the HLA-B44 supertype ( 35 ). B12C is a CREG shared by B12 (B44 and B45), B13, B21 (B49 and B50), B37, B40 (B60 and B61), B41, and B47 ( 32 – 34 ).…”

“…Among B12C, several disease-associated alleles/antigens are gathered, for instance, B13 and B37 (psoriasis), B40 (acute lymphatic leukemia), B41 (hepatitis), and B47 (adrenogenital syndrome), and there is a strong overlap with the HLA-B44 supertype characterized by particular peptide binding properties ( 8 ). The B and F pockets’ binding specificities for acidic and aromatic/aliphatic/hydrophobic amino acid residues, respectively ( 8 ), may be involved in a rather reduced binding capability of otherwise immunogenic HPV16 E6 and E7 peptides ( 35 ).…”

Analogies between HPV Behavior in Oral and Vaginal Cavity: Narrative Review on the Current Evidence in the Literature

“…This finding is strengthened by other manuscripts that have correlated HLA-G expression and poor prognosis [ 61 , 62 ]. These data are consistent with other HLA class I polypeptides [ 45 , 46 ] and with other class II polypeptides [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ], but also with patients with squamous cell carcinoma of the head and neck [ 21 , 70 ].…”