Dear All

I would like to invite you to the next Nencki Institute seminar which will take place on Thursday 16th of March at 3pm in the CN lecture hall. We will host Dr Mitrajit Ghosh a PASIFIC Fellow from the Laboratory of Molecular Neurobiology led by prof. Bożena Kamińska. Dr. Gosh will give a lecture enitled: Heterogeneity and plasticity tumour associated astrocytes in murine gliomas as defined by immunohistochemistry and spatial transcriptomics.

Abstract 

Compelling evidence shows that the composition of the tumour microenvironment (TME) modulates tumour progression and impacts therapy outcomes. The most aggressive and deadly primary brain tumours in adults are glioblastoma (GBM). Despite multimodal therapy including neurosurgery, radiation therapy and chemotherapy, the median survival of glioblastoma patients treated remains 15-16 months. GBM is one of the most immunosuppressed and heterogeneous tumors. Inter and intra-tumoral heterogeneity is a major hurdle for precise diagnosis and treatment of brain tumour patients. TME heterogeneity due to heavy infiltration of immunosuppressive myeloid cells, activation of astrocytes and endothelial cells might contribute to tumour progression, treatment resistance and relapse. Therefore, we sought to understand spatial heterogeneity of astrocytes in a mouse model of GBM.

We optimised the protocol for spatial transcriptomics (Visium, 10x Genomics) on fresh frozen sections of murine brains bearing intracranial GL261 gliomas and combined it with multiple immunohistochemistry (IHC) staining for detailed characteristics of mouse glioma TME. Deconvolution of TME was performed with public single-cell (sc) RNAseq datasets from GL261 gliomas. We decoded several structural and functional clues allowing us to dissect functionalities of tumour-associated astrocytes at distinct locations within TME. The analysis of morphology and location of astrocytes demonstrated their heterogeneity and various roles in shaping the local tumour microenvironment and revealed potential contributing factors. We demonstrated that the therapeutic intervention targeting glioma-myeloid cell interactions via integrins and aiming to convert “cold” into “hot” TME impacted the spatial distribution of astrocytes in murine gliomas.

Integration of single-cell and spatial transcriptomics combined with multi marker IHC revealed the tumour heterogeneity and substantial changes in astrocytes surrounding experimental gliomas. We show that the heterogeneous population of tumour-associated astrocytes could be an important therapeutic target. These findings provide a rationale for developing novel combinatorial treatments to improve anti-glioma therapies.

The seminar will be followed by a get together.
With best regards
Aleksandra Pękowska