Abstract A060: Reactive oligodendrocytes promote glioblastoma progression through CCL5/CCR5-mediated glioma stem cell maintenance
Bibliographic record
Abstract
Abstract Glioblastoma (GBM) thrives in an ecosystem that is shaped by intricate intercellular interactions that contribute to tumor progression and treatment resistance. Recent studies have shown that the oligodendrocyte lineage (OL) is abundantly enriched in the GBM tumor microenvironment. In this study, we utilized single-cell RNA sequencing (scRNA-seq) profiles from 120 primary and recurrent GBM tumors, spatial transcriptomics, immunohistochemistry, cytokine profiling, and in vitro migration assays to demonstrate that OLs are selectively recruited to the GBM tumor border, and subsequently incorporated into the tumor mass at recurrence. Using a pan-disease single-cell human OL meta-atlas, we identified a population of malignancy-associated reactive OLs, akin to those seen in demyelinating inflammatory and traumatic conditions. The interferon-mediated induction of this population was validated using in vivo GL261 and CT2A syngeneic mouse models. Cytokine profiling and ligand-receptor (LR) interaction analyses identified several pro-tumorigenic cytokines secreted by reactive OLs, including CCL5. Moreover, we found that CCR5, the CCL5 receptor, was preferentially expressed in glioma stem-like cells (GSCs) and upregulated at recurrence. Targeting CCR5 in GBM tumor cells with genetic knockdown or pharmacological inhibition impaired GSC stemness and prolonged the survival of mice bearing GBM tumors. Our work highlights the functional interplay between OLs and GBM cells and positions the CCL5/CCR5 axis as a druggable target for GBM. Citation Format: Jason Moffat. Reactive oligodendrocytes promote glioblastoma progression through CCL5/CCR5-mediated glioma stem cell maintenance [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A060.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".