Multimodal profiling of chordoma immunity reveals distinct immune contextures

• DOI: 10.1101/2023.09.14.557579
• Publication Date: 2023-09-17T21:10:13Z
• Authors: S. van Oost; D.M. Meijer; M.E. IJsselsteijn; J. Roelands; B. van den Akker; R. van der Breggen; I.H. Briaire-de B...; M. van der Ploeg; P.M. Wijers-Koster; S.B. Polak; W.C. Peul; R.J.P. van der Wal; N.F.C.C. de Miranda; J.V.M.G. Bovee
• Keywords: Immunophenotyping; Infiltration (HVAC); Chordoma

Abstract Chordomas are cancers from the axial skeleton presenting immunological hallmarks of unknown significance. In recent years, some clinical trials demonstrated that chordomas can respond to immunotherapy. We present a comprehensive characterisation features 76 through application multimodal approach comprising transcriptional profiling, multidimensional immunophenotyping and TCR profiling. generally presented an immune “hot” microenvironment in comparison other sarcomas, as indicated by immunologic constant rejection signature. identified two distinct groups based on T cell infiltration. The highly infiltrated group was further characterised high dendritic infiltration presence multicellular aggregates tumours, whereas low associated with lower overall densities stromal cells. Interestingly, patients higher displayed more pronounced clonal enrichment receptor repertoire compared those counts. Furthermore, we observed majority maintained HLA class I expression. Our findings shed light natural immunity against chordomas. Understanding their landscape could guide development immunotherapies tailored manner, ultimately leading improved outcome for chordoma patients.