Spatial single-cell profiling of deeply matched extreme long-term surviving glioblastoma patients reveals a distinct immune and stem cell driven ecosystem
Abstract
Abstract Inter- and intratumoral heterogeneity have been suggested to substantially contribute to variations in tumoral behavior and survival in Glioblastoma (GBM). However, the exact contribution of the interplay between cancer cells and their microenvironment remains poorly understood. From a cohort of 2632 GBM patients, we selected 12 extreme long-term GBM survivors (eLTS, survival over 10 years) and 22 rigorously clinically matched short-term survivors (STS, survival less than 20 months). We compared the spatial composition and cellular interactions within the tumor microenvironment using high-dimensional, multiplexed immunofluorescence and spatial transcriptomics. Through extensive data analysis, we identified a specific perivascular niche in STS patients marked by a strong enrichment of the immunosuppressive milieu featuring CD133+ Glioma Stem Cells (GSCs), alternatively activated HMOX1high/PDL1high macrophages (MFs), and exhausted T-cytotoxic lymphocytes (Tcyts). By contrast, eLTS patients were characterized by an enrichment of immunocompetent HLA-DRhigh MFs and Tcyts that infiltrate deep into the tissue. Our work offers insights into the unique stem cells and immunosuppressive-driven ecosystems that underlie substantial differences in survival in GBM patients.
Authors 29
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Brecht Decraene corresponding
Universitair Ziekenhuis Leuven · KU Leuven
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University Hospitals Leuven & KU Leuven
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KU Leuven
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KU Leuven
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Universitair Ziekenhuis Leuven
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University Hospitals Leuven
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Universitair Ziekenhuis Leuven · KU Leuven
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KU Leuven
KU Leuven Lien Spans University Hospitals Leuven
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Universitair Ziekenhuis Leuven
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University Hospitals Leuven
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Universitair Ziekenhuis Leuven · KU Leuven
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KU Leuven
KU Leuven Lien Solie University Hospitals Leuven
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Universitair Ziekenhuis Leuven
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University Hospitals Leuven
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KU Leuven
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KU Leuven
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KU Leuven
KU Leuven Raf Sciot KU Leuven
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KU Leuven
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KU Leuven
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KU Leuven
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Universitair Ziekenhuis Leuven
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University Hospitals Leuven
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Universitair Ziekenhuis Leuven
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University Hospitals Leuven
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KU Leuven
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VIB-KU Leuven Center for Microbiology · KU Leuven
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KU Leuven - VIB
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Jessa Hospital
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Cliniques Universitaires Saint-Luc · Radboud University Nijmegen · Radboud University Medical Center
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Radboud University Medical Centre
Radboud University Medical Centre Bonny Noens St Lucas Hospital Johnny Duerinck University Hospitals Brussels
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St Lucas Hospital
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University Hospitals Brussels
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Gert De Mulder Aachen
Leiden University Medical Center · Ziekenhuis Oost-Limburg
Affiliation as printed
Ziekenhuis Oost-Limburg
Leiden University Medical Center
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Frank J. M. Weyns Aachen
Leiden University Medical Center · Ziekenhuis Oost-Limburg
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Ziekenhuis Oost-Limburg
Leiden University Medical Center
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Marike L. D. Broekman Aachen
Leiden University Medical Center
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Leiden University Medical Center
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Newcastle University
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KU Leuven
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KU Leuven
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Affiliation as printed
KU Leuven
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