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000305509 1001_ $$aCakmak, Pinar$$b0
000305509 245__ $$aSpatial immune profiling defines a subset of human gliomas with functional tertiary lymphoid structures.
000305509 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2025
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000305509 500__ $$a2025 Nov 11;58(11):2847-2863.e8
000305509 520__ $$aAdult-type diffuse gliomas, the most common primary brain tumors, respond poorly to immune-based therapies and are considered immunologically 'cold' tumors. Here, we examined the features and clinical relevance of glioma intratumoral tertiary lymphoid structures (TLSs) using spatial transcriptome and proteome profiling. In a cohort of 642 gliomas, TLSs were present in 15% of tumors and associated with a remodeled perivascular space and spatial redistribution of extracellular matrix components. Three distinct TLS subtypes could be defined based on differing cellular composition and immune activity. While all subtypes lacked classical germinal center architecture, certain TLSs exhibited features of dynamic immune functions, including clonal T and B cell expansion, generation of IgA⁺ and IgG⁺ plasma cells, and dendritic cell-T cell interactions. The presence of TLSs with active immune response features correlated with improved overall survival. Thus, a functional adaptive immune response is detectable in some gliomas, with implications for stratification and treatment.
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000305509 650_7 $$2Other$$aB cells
000305509 650_7 $$2Other$$aadaptive immune receptor repertoire
000305509 650_7 $$2Other$$aadult-type diffuse glioma
000305509 650_7 $$2Other$$ablood-brain barrier
000305509 650_7 $$2Other$$aglioblastoma
000305509 650_7 $$2Other$$aimmune aggregate
000305509 650_7 $$2Other$$aspatial molecular profiling
000305509 650_7 $$2Other$$aspatial transcriptomics
000305509 650_7 $$2Other$$atertiary lymphoid structures
000305509 650_7 $$2Other$$atumor immunology
000305509 7001_ $$aLun, Jennifer H$$b1
000305509 7001_ $$aSingh, Aakanksha$$b2
000305509 7001_ $$aMacas, Jadranka$$b3
000305509 7001_ $$aSchupp, Jonathan$$b4
000305509 7001_ $$aSchuck, Jonas$$b5
000305509 7001_ $$aMahmoud, Zeina$$b6
000305509 7001_ $$aKöhler, Miriam$$b7
000305509 7001_ $$aStarzetz, Tatjana$$b8
000305509 7001_ $$aBurger, Michael C$$b9
000305509 7001_ $$0P:(DE-HGF)0$$aSteidl, Eike$$b10
000305509 7001_ $$aHasse, Lucie Marie$$b11
000305509 7001_ $$0P:(DE-HGF)0$$aHattingen, Elke$$b12
000305509 7001_ $$0P:(DE-HGF)0$$aPlate, Karl H$$b13
000305509 7001_ $$0P:(DE-HGF)0$$aReiss, Yvonne$$b14
000305509 7001_ $$aImkeller, Katharina$$b15
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