Research > Focus B > Work Packages B04

Impact of myeloid cells on the adaptive immune response in IDH1-mutant glioblastomas

Summary

In this project, we will characterize the potential immunosuppressive role of myeloid cells for T-cell based immune response in isocitrate dehydrogenase (IDH)1 mutant glioblastomas. We will particularly focus on radio- or chemotherapy-induced changes of the immune tumor microenvironment and how this can be improved pharmacologically. We hypothesize that influencing the composition of the intratumoral myeloid compartment might help to better control pre-existing and therapy-induced immunosuppression. The visual abstract below shows the aims and planned tasks of the work package.

Task 1

Characterization of TAMs and TILs

to provide information about major TAM and TIL subsets, their abundance and interaction, treatment- related changes in recurrent tumors and their clinical relevance
to identify novel markers and targets on TAMs to be employed in future diagnosis and treatment of IDH1mut gliomas

Steps / Workflow

IDH1mut newly diagnosed and recurrent glioma with/without RT or CT

cells
- isolation of TAM, TIL, EC
- scRNAseq
tissues
- multicolor IF stainings (TAM / TIL)
- novel TAM / TIL subsets by IF or smFISH
- RNAseq

Task 2

Unravel metabolic determinants of response and resistance to checkpoint blockade

Steps / Workflow

TAM secretome
TAM – T-cell interaction
- TIL secretome / subset
- T-cell transmigration
- T-cell killing
TAM targeting
- TAM secretome / subset
- TAM transcriptome
- TIL phenotype
- T cell functionality