Impact of oncogenic IDH mutation on the extracellular matrix to mediate immune evasion in glioma

Gliomas with oncogenic IDH mutations (IDHmut) are characterized by an immunosuppressive microenvironment and an aberrant extracellular matrix (ECM). We hypothesize that IDHmut drives specific glioma cell states that actively secrete fibronectin (FN1), tenascin-C (TNC), and other ECM components, mediating immune evasion. Using spatial transcriptomics, proteomics, and atomic force microscopy, we will map ECM–immune–tumor interactions in human glioma (Aim 1). Organoid models will track temporal dynamics (Aim 2), and in vivo perturbations will test FN1 and TNC function (Aim 3).