Dataset Information

The Immunopeptidomic Landscape of Ependymomas provide actionable antigens for T cell-based immunotherapy

ABSTRACT: Ependymoma (EPN) are primary tumors of the nervous system. Due to their growth pattern, most ependymoma can be managed with neurosurgical resection alone. A substantial proportion of these tumors recurs or display infiltrative growth pattern, however. Therapeutic options after neurosurgical resection are limited. Based on tumor board recommendations, radiation therapy will be recommended for some patients. Systemic treatment options for progressive ependymoma include platin-based therapeutic regimes or a combination of lapatinib and temozolomide. Peptide-based immunotherapy represents a promising low-side effect therapeutic option relying on the induction of tumor-specific T cells targeting human leukocyte antigens (HLA)-presented peptides. We here analyzed the landscape of naturally presented HLA class I and II ligands of primary ependymomas using a comparative mass-spectrometry-based immunopeptidomic approach to delineate naturally presented ependymoma-associated antigens. We discovered a subset of EPN-exclusive peptides including HLA-A*02 and HLA-A*25/HLA-A*26–restricted HLA ligands and identified a small panel of cancer/testis antigens (CTAs)-derived HLA ligands. Furthermore, we outlined immunopeptidomic alterations in different EPN-subgroups and progressive EPNs and performed subsequent functional characterization for demonstrating immunogenicity in vitro. Taken together, we provide actionable targets that could further be explored as a T-cell based immunotherapeutic strategy in this tumor entity.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Central Nervous System

SUBMITTER: Jonas Scheid

LAB HEAD: Juliane Walz

PROVIDER: PXD052448 | Pride | 2025-05-26

REPOSITORIES: Pride

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			Action	DRS
	171213_LM_Ependymoma_256-17_Tumor_Tue39L243_20_Rep1_25cm90min3s_msms31.msf	Msf
	171213_LM_Ependymoma_256-17_Tumor_Tue39L243_20_Rep1_25cm90min3s_msms31.raw	Raw
	171213_LM_Ependymoma_256-17_Tumor_Tue39L243_20_Rep2_25cm90min3s_msms32.msf	Msf
	171213_LM_Ependymoma_256-17_Tumor_Tue39L243_20_Rep2_25cm90min3s_msms32.raw	Raw
	171213_LM_Ependymoma_256-17_Tumor_Tue39L243_20_Rep3_25cm90min3s_msms33.msf	Msf

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The immunopeptidomic landscape of ependymomas provides actionable antigens for T-cell-based immunotherapy.

Mühlenbruch Lena L Rieger David D Becker Hannes H Santos Leite Ana Maia AM Mäurer Irina I Schittenhelm Jens J Dubbelaar Marissa M Bichmann Leon L Kohlbacher Oliver O Rammensee Hans-Georg HG Gouttefangeas Cécile C Tatagiba Marcos M Walz Juliane S JS Tabatabai Ghazaleh G

Neuro-oncology advances 20250116 1

<h4>Background</h4>Ependymoma are primary tumors of the nervous system. Due to their growth pattern, many ependymomas can be managed with neurosurgical resection alone. A substantial proportion of these tumors recurs or displays infiltrative growth patterns. Further established therapeutic options include radiation therapy. Systemic treatment options include platinum-based therapeutic regimes or a combination of lapatinib and temozolomide. Peptide-based immunotherapy represents a promising thera ...[more]

PMID: 40376681

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Project description:Various cancer immunotherapies rely on the T cell 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 (FDR) approach. First application of the database provided insights into the representation of cancer-testis antigens (CTA) across malignant and benign tissues and enabled the identification and characterization of the 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. 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 the 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.