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
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract