Using spatial multiomics, Cakmak et al. profiled 642 adult-type diffuse gliomas and identified tertiary lymphoid structures (TLSs) in 15% of the tumors. TLS-positive gliomas showed decreased neural tumor signatures, and were associated with vascular and extracellular matrix remodeling. Three distinct TLS subtypes – T-low-TLS (low T cell abundance), B:T-TLS (B and T cells interaction), and PC-TLS (plasma cell-rich) – with different cellular compositions and immune functions were identified. B:T-TLS and PC-TLS showed lymphocyte clonal expansion, plasma cell differentiation, and DC–T cell interactions, and were associated with increased survival.
Contributed by Shishir Pant
ABSTRACT: Adult-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.
Author Info: (1) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany. (2) Goethe Univers
Author Info: (1) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany. (2) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany. (3) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany. (4) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany. (5) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany. (6) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany. (7) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany. (8) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany. (9) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany. (10) Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany; Goethe University, University Hospital, Dr. Senckenberg Institute of Neurooncology, Frankfurt, Germany. (11) University Cancer Center (UCT), Frankfurt, Germany; Goethe University, University Hospital, Institute of Neuroradiology, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany. (12) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany. (13) Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany; Goethe University, University Hospital, Institute of Neuroradiology, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany. (14) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany. (15) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany. (16) Goethe University, University Hospital, Institute of Neurology (Edinger Institute), Frankfurt, Germany; Frankfurt Cancer Institute (FCI), Frankfurt, Germany; University Cancer Center (UCT), Frankfurt, Germany. Electronic address: imkeller@rz.uni-frankfurt.de.
