gms | German Medical Science

Objective: Although meningioma are amongst the most common intracranial tumors, available treatment options beyond surgery and radiotherapy are virtually not existent. However, in many cases surgery alone is not sufficient (e.g. meningeomatosis, recurrence, infiltration, challenging localisation). T-cell based immunotherapy is a promising approach in Neuro-Oncology, but immunological strategies require a deep understanding of a tumor’s antigenic landscape. The focus of this project is to map the yet unknown antigenic profile of meningioma by sequencing the natural Human Leukocyte Antigen (HLA) ligandome of meningioma in order to find tumor-associated peptides as immunotherapeutic targets for peptide vaccination

Methods: We collected tumor tissue from patients operated at our Neurosurgical Department. The tumor tissue was snap-frozen and lysed to isolate HLA-peptides by using immunoprecipitation. The Peptide samples were then separated by reversed-phase liquid chromatography and analyzed by mass spectrometer. The measured peptides were then compared against a normal human tissue dataset to identify tumor-specific ones.

Results: We present the analysis of HLA-presented peptidome of meningioma. Based on the analysis of patient samples (n=28) covering different WHO grades, we performed comparative HLA peptidome profiling against a dataset of normal human tissues. Using an immunopeptidome-centric approach, we could clearly delineate a subset of naturally presented, Meningioma-associated and -exlusive HLA ligands derived from proteins with a Cancer-Testis-Antigen Gene-Expression-Profiles (n=36). Amongst them, we discovered that the cancer antigens MAGEC-2, PIWIL1, DNAJB8 and AKAP-4 (previously described in other cancers) are also expressed ion meningioma and therefore are potential immunotherapeutic targets in meningioma.

Conclusion: This research work is meant to lay the foundation for future efforts to translate tumor-associated-antigen driven T-cell based immunotherapeutic approaches in neuro-oncology. Until now, the HLA-lLigandome of meningioma was completely unknown. However, antigens, which are tumor-exclusive and ideally are recognized by T-cells, are thought to be excellent targets for immunotherapeutic approaches. We were able to analyze the meningioma HLA-Ligandome and found that known Cancer-Antigens MAGEC-2, AKAP-4, DNAJB8 and PIWIL1 are also expressed in meningioma. These antigens are potential immunotherapeutic T-cell targets in meningioma and candidates for peptide vaccination.

Figure 1 [Fig. 1]