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Updated: Jun 18, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Cranioencephalic functional lymphoid units in glioblastoma
Celia Dobersalske1,2,3, Laurèl Rauschenbach1,3,4,5,6, Yichao Hua7
1German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, a partnership between DKFZ and University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Insights
Cranial bone marrow near glioblastoma tumors contains active CD8+ T cells that fight cancer. This discovery suggests preserving this bone marrow may improve glioblastoma treatment outcomes.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- Glioblastoma microenvironment is often considered immunosuppressed.
- Limited understanding of immune cell presence in cranial bone marrow adjacent to tumors.
Purpose of the Study:
- To investigate lymphoid populations in cranial bone marrow of glioblastoma patients.
- To identify immune cell characteristics and their association with tumor response.
Main Methods:
- Analysis of clinical cell and tissue specimens from glioblastoma and control patients.
- Utilized clinical imaging, single-cell profiling, and immune cell quantification.
- Assessed T cell clonotypes, effector types, and lymphoid egress markers.
Main Results:
- Active lymphoid populations, including tumor-reactive CD8+ T cells, found in cranial bone marrow near glioblastoma.
- Identified CD8+ effector T cells expressing S1PR1 in the tumor-proximal CB niche.
- Cranial CXCR4 enhancement correlated with improved progression-free survival.
Conclusions:
- Cranial bone marrow harbors active, tumor-reactive T cells at glioblastoma diagnosis.
- These findings challenge the notion of a fully immunosuppressed tumor ecosystem.
- Suggests exploiting cranioencephalic immune units for glioblastoma therapy.
Abstract:
The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8+ T cell clonotypes in the CB that were also found in the tumor. These were characterized by acute and durable antitumor response rooted in the entire T cell developmental spectrum. In contrast to distal bone marrow, the CB niche proximal to the tumor showed increased frequencies of tumor-reactive CD8+ effector types expressing the lymphoid egress marker S1PR1. In line with this, cranial enhancement of CXCR4 radiolabel may serve as a surrogate marker indicating focal association with improved progression-free survival. The data of this study advocate preservation and further exploitation of these cranioencephalic units for the clinical care of glioblastoma.
