> Details

Medici, Gioele; Wacker, Marcel; Dubbelaar, Marissa; Schwitalla, Carolin; Hanssen, Friederike; Schulz, Daniel; Vasella, Flavio; Rushing, Elisabeth; Bauer, Jens; Bodenmiller, Bernd; Rammensee, Hans-Georg; Regli, Luca; Walz, Juliane; Weller, Michael; Neidert, Marian

IMMU-28. THE INTRA-TUMORAL SPATIAL HETEROGENEITY OF T CELL ANTIGENS IN GLIOBLASTOMA: AN INTEGRATED MULTI-OMICS APPROACH

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: IMMU-28. THE INTRA-TUMORAL SPATIAL HETEROGENEITY OF T CELL ANTIGENS IN GLIOBLASTOMA: AN INTEGRATED MULTI-OMICS APPROACH
  • Contributor: Medici, Gioele; Wacker, Marcel; Dubbelaar, Marissa; Schwitalla, Carolin; Hanssen, Friederike; Schulz, Daniel; Vasella, Flavio; Rushing, Elisabeth; Bauer, Jens; Bodenmiller, Bernd; Rammensee, Hans-Georg; Regli, Luca; Walz, Juliane; Weller, Michael; Neidert, Marian
  • Published: Oxford University Press (OUP), 2022
  • Published in: Neuro-Oncology, 24 (2022) Supplement_7, Seite vii137-vii137
  • Language: English
  • DOI: 10.1093/neuonc/noac209.525
  • ISSN: 1522-8517; 1523-5866
  • Keywords: Cancer Research ; Neurology (clinical) ; Oncology
  • Origination:
  • Footnote:
  • Description: Abstract This study investigates the intratumoral heterogeneity of T cell antigen presentation in 15 newly diagnosed glioblastoma patients. Our multi-omics approach includes mass spectrometry-based immunopeptidome analysis, next-generation sequencing (whole-exome and RNA sequencing), and imaging mass cytometry performed on biopsies deriving from the necrotic core (NEC), the gadolinium contrast-enhancing region (T1), and the peritumoral infiltrating zone (INF, 5-ALA positive). A total of 24493 unique HLA class I and 17394 unique HLA class II peptides were identified. Comparative profiling of peptides from our study and a benign tissue database (in-house; n = 429 donors combined with HLA ligand atlas (https://hla-ligand-atlas.org)) revealed that 20% of HLA class I ligands are glioblastoma exclusive. Of these ligands, 21%, 21%, and 15% were exclusively presented in the INF, T1, or NEC zone, respectively. Here, we focused on the INF-specific antigens as this zone is likely to remain after tumor resection and gives rise to glioblastoma recurrence. Interestingly, two INF-specific HLA ligands showed a frequency presentation of 45% in our patient cohort. One ligand originated from BAALC (Brain and acute leukemia cytoplasmic protein) and one from NCAN (Neurocan core protein), which are both known to be glioblastoma-associated proteins. Immunogenicity of pre-selected candidate antigens was assessed with autologous expanded T cells and revealed a set of novel promising targets for immunotherapy. Integrated RNA/DNA sequencing also enabled the identification of neoepitopes deriving from tumor- and region-specific mutations. Furthermore, imaging mass cytometry contributed to investigating the immune compartment of the tumor microenvironment in high dimensionality and spatial resolution. In conclusion, our approach characterized the intra-tumoral regional heterogeneity of both infiltrating immune cells and tumor antigens. This multi-omics spatial atlas of the immune landscape can be used for the informed design of immunotherapy strategies against glioblastoma.
  • Access State: Open Access