DIPG is the deadliest paediatric brain tumour and all efforts for DIPG treatment have proved to be unsuccessful and with median survival rate of only 9 months after diagnosis, there is an urgent need for viable options for treatment of DIPG. Cancer immunotherapy is an emerging approach to treat untreatable cancers. The key mechanism by which the adaptive immune system combats cancer is by recognizing the peptides presented on the surface of the tumour in complex with the Human Leukocyte Antigen (HLA) molecules. Knowledge of the peptide repertoire presented by HLA molecules holds the key to unlock target-specific cancer immunotherapies like vaccines and adoptive T-cell therapies. The recent advances in mass spectrometry, proteomics and bioinformatics have made it possible to characterize the HLA immunopeptidome of tumour cells.
However, the classical HLA class-I antigens tend to be downregulated in human tumour pathology, preventing the tumour-derived peptides from being presented to the immune system. This is one of the mechanisms which allows tumour cells to escape lysis by cytotoxic immune cells. In addition, an upregulation of the immune inhibiting non-classical HLA molecules, HLA-G and HLA-F was observed in tumours and due to limited peptide repertoire of HLA-G and HLA-F, we chose to study the immunopeptidome of HLA- G and HLA-F in DIPG cell lines to identify potential immunotherapeutic targets.
We engineered DIPG cell lines to exclusively express only HLA-G / HLA-F which was measured by flow cytometry. Through Immunopeptidomic approaches, we were able to isolate peptides restricted to HLA-G and HLA-F which were derived from known cancer testis antigen sources. Although the immunopeptidome data was limited due to limited cell numbers, these data suggest that the peptides derived from HLA-G and HLA-F have the potential to enhance immunotherapy efficacy in treating DIPG with further research and in-depth analysis of the peptides obtained.