Abstract B013: Evaluating Chi3L1 as a potential target for immunotherapy in chordoma
Bibliographic record
Abstract
Abstract Introduction: Chordoma, a rare yet highly morbid cancer arising from notochordal progenitor cells along the spinal axis, currently depends on surgical resection and radiation, with no effective therapies once those options are exhausted. Chitinase-3-Like 1 (Chi3L1), a secreted glycoprotein expressed in immune cells, has been shown to suppress PD-1-mediated T-cell activation and promote epithelial-mesenchymal transition (EMT), making it a compelling immunotherapeutic target. Preliminary RNA sequencing and NanoString data demonstrate Chi3L1 expression in human chordoma tissue and patient-derived cell lines, and its role in maintaining a mesenchymal and potentially cancer stem cell (CSC)-like phenotype in chordoma is under investigation. Methods: We evaluated Chi3L1 expression in commercially available chordoma cell lines and intraoperatively collected primary human sacral chordoma samples. Protein and RNA analyses (Western blot, qPCR, RNA-Seq) were performed on these samples. To study immune modulation, peripheral blood mononuclear cells (PBMCs) were isolated from patient blood samples and treated in vitro with an anti-Chi3L1 monoclonal antibody (FRG). In parallel, FRG is being incorporated into a biodegradable hydrogel for localized delivery to tumor cells. We are also conducting in vivo experiments using immunocompromised mice implanted with human chordoma cells to evaluate the therapeutic efficacy of hydrogel-based FRG delivery and its impact on CSC markers and tumor growth. Results: Our findings show elevated Chi3L1 expression in primary and recurrent chordoma cell lines compared to notochordal controls. Patient-derived cell lines demonstrated particularly high levels of Chi3L1 secretion. Early data from PBMC co-culture experiments suggest that FRG treatment may restore immune activation suppressed by Chi3L1. Ongoing in vivo studies using immunocompromised mice aim to assess the therapeutic potential of FRG-loaded hydrogel in suppressing tumor growth and targeting CSC-like phenotypes. Conclusion: Elevated Chi3L1 expression and secretion in chordoma cells, along with its immunosuppressive and EMT-promoting effects, highlight its potential as a therapeutic target. Use of FRG antibody, both in vitro and via localized hydrogel delivery, may provide a novel strategy to disrupt tumor immune evasion and reduce CSC-like properties. In vivo experiments in immunocompromised mice will further define the role of Chi3L1 in chordoma progression and therapy resistance. Citation Format: Jessica Ding, Kaylee M. Gallagher, Beatrice Campilan, Christian Godinez, Christian Schroeder, Tianyi Wang, Ziya Gokaslan, Patricia Sullivan, Margot Martinez-Moreno. Evaluating Chi3L1 as a potential target for immunotherapy in chordoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr B013.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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 teacher head, 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".