Immunotherapeutic strategies are increasingly important in neuro-oncology and the elucidation of escape mechanisms which lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing wildtype and PD-1-/- mice survived significantly longer than immunodeficient Pfp/Rag2-/- mice. While tumors in Pfp/Rag2-/- mice were highly polyclonal, immunoedited tumors in WT and PD-1-/- mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in wildtype mice were distinguished by an interferon-gamma-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even stronger to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, cancer immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas. SOURCE: Cecile,Laure,Maire (cmaire@uke.de) - Laboratory for Brain Tumor Biology University Medical Center Hamburg-Eppendorf

Pluto Bioinformatics

GSE151284: Glioma escape signature and clonal development under immune pressure [RNA-Seq]