Abstract 4030
Background
In Germany, approximately 30-50% of Oropharyngeal squamous-cell carcinoma (OPSCC) are related to human papillomaviruses (HPV), of which 90% are caused by HPV-16. The analysis of cancer-associated antigens is needed to develop antigen-specific immunotherapy and to determine the level of personalization required for therapeutic cancer vaccines.
Methods
Human leucocyte antigen (HLA) ligands from fresh frozen OPSCC biopsies were analyzed. HLA molecules were extracted from tumor tissue using immunoaffinity chromatography. HLA-bound peptides were subjected to high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS). Tumor-exclusive antigens in OPSCC were identified by comparative profiling against an in-house benign and malignant database. Additionally, whole exome sequencing of RNA and DNA isolated from the respective cancer biopsies was performed to complement the database.
Results
To date, HLA ligandomes from 28 OPSCC (15 HPV+; 13 HPV-) patients were analyzed. Compared to the benign samples database, 148 source proteins were tumor-exclusive for HLA class I and 200 source proteins for HLA class II. The mean number of tumor-exclusive proteins per sample was 6.0 (0-14) for HLA class I and 7.7 for HLA class II (0-41) respectively. Among the tumor exclusive proteins for HLA class I, 23 had not been detected in other malignant tumor ligandomes (n = 703 samples) and 75 for HLA class II (n = 433 samples). A principal component analysis of the HLA-ligandomes from HPV+ and HPV- revealed significant differences between the two groups. For HLA-class I, 85 tumor-exclusive proteins were only found in HPV+ and 55 in HPV-, whereas 8 proteins were found in both groups. Among the 200 HLA class II tumor-exclusive proteins, 96 were only found in HPV+ and 95 in HPV- respectively, whereas 9 were shared by HPV+ and HPV-.
Conclusions
The analysis of HLA-ligandomes from OPSCC revealed tumor-exclusive and newly discovered antigens. We found clear differences between the HLA ligandomes of HPV+ and HPV- patients. These differences need to be taken into account for therapeutic vaccination strategies. The level of personalization needed for such vaccines remains to be determined.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
University of Ulm, Clinician Scientist Programme.
Disclosure
S. Laban: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme (MSD); Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (institution): Merck Serono. P.J. Schuler: Advisory / Consultancy: Bristol-Myers Squibb. T.K. Hoffmann: Honoraria (institution), Advisory / Consultancy: Merck Sharp & Dohme (MSD); Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Merck Serono. H. Rammensee: Advisory / Consultancy, Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Immatics; Advisory / Consultancy, Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: CureVac; Advisory / Consultancy, Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Synimmune. All other authors have declared no conflicts of interest.
Resources from the same session
2743 - The Impact of Targeted Therapies and Immunotherapy in Melanoma Brain Metastases: a Systematic Review and Meta-Analysis
Presenter: Mario Mandala
Session: Poster Display session 3
Resources:
Abstract
5479 - Intracranial Anti-Tumor Activity in Melanoma Brain Metastases with Encorafenib Plus Binimetinib: A Multicenter, Retrospective Analysis
Presenter: Jose Lutzky
Session: Poster Display session 3
Resources:
Abstract
3560 - Outcomes of Patients with Melanoma Brain Metastases (MBM) Treated with Standard of Care Therapy After Being Excluded from MBM-Specific Clinical Trials
Presenter: Kourtney Holbrook
Session: Poster Display session 3
Resources:
Abstract
3175 - The analysis of current treatment outcomes in melanoma patients with brain metastases
Presenter: Joanna Placzke
Session: Poster Display session 3
Resources:
Abstract
4550 - A multivariate model to define prognostic groups among patients with melanoma brain metastases: a 10-year retrospective cohort study
Presenter: Giacomo Pelizzari
Session: Poster Display session 3
Resources:
Abstract
4191 - The immune landscape of melanoma significantly influences survival in patients with highly mutated tumors.
Presenter: Robert Ferguson
Session: Poster Display session 3
Resources:
Abstract
1625 - Final Results from Phase II of Combination with Canerpaturev (formerly HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Unresectable or Metastatic Melanoma in 2nd-or later line treatment
Presenter: Kenji Yokota
Session: Poster Display session 3
Resources:
Abstract
5346 - Evaluating polygenic risk score prediction model for melanoma prognosis
Presenter: Miriam Potrony
Session: Poster Display session 3
Resources:
Abstract
5477 - Impact of sarcopenia in patients with metastatic melanoma treated with immunotherapy
Presenter: Maria Grazia Vitale
Session: Poster Display session 3
Resources:
Abstract
3469 - Ancillary evaluation of systemic immune antitumor response (SIAR) and tumor growth rate (TGR) of patients (pts) with metastatic melanoma (MM) treated with radiotherapy (RT) combined with ipilimumab (ipi) in the phase 1 study Mel-Ipi-Rx.
Presenter: Celine Boutros
Session: Poster Display session 3
Resources:
Abstract