PCI-DB: A novel primary tissue immunopeptidome database to guide next-generation peptide-based immunotherapy development

Various cancer immunotherapies rely on the T cell-mediated recognition of peptide antigens presented on human leukocyte antigens (HLA). However, the identification and selection of naturally presented peptide targets for the development of personalized as well as off-the-shelf immunotherapy approaches remains challenging. Here, we introduce the open-access Peptides for Cancer Immunotherapy Database (PCI-DB, https://pci-db.org/), a comprehensive resource of immunopeptidome data originating from various malignant and benign primary tissues that provides the research community with a convenient tool to facilitate the identification of peptide targets for immunotherapy development. The PCI-DB includes > 6.6 million HLA class I and > 3.4 million HLA class II peptides from over 40 tissue types and cancer entities analyzed uniformly using high-sensitive nf-core bioinformatics pipelines and applying a global peptide false discovery rate. First application of the database provided insights into the representation of cancer-testis antigens across malignant and benign tissues, enabling the identification and characterization of cross-tumor entity and entity-specific tumor-associated antigens as well as naturally presented neoepitopes from frequent cancer mutations. Further, we used the PCI-DB to design personalized peptide vaccines for two patients suffering from metastatic cancer. In a retrospective analysis, PCI-DB enabled the composition of both a multi-peptide vaccine comprising non-mutated, highly frequent tumor-associated antigens matching the immunopeptidome of the individual patient´s tumor and a neoepitope-based vaccine matching the mutational profile of a cancer patient. Both vaccine approaches induced potent and long-lasting T-cell responses, accompanied by long-term survival of these advanced cancer patients. In conclusion, the PCI-DB provides a highly versatile tool to broaden the understanding of cancer-related antigen presentation and, ultimately, supports the development of novel immunotherapies.