Abstract B024: TrkB.T1 receptor promotes an immunosuppressive microenvironment driven by neutrophil recruitment in gliomas
Bibliographic record
Abstract
Abstract Gliomas are the most common type of brain tumor in both children and adults. Communication between cancer cells and the brain tumor microenvironment (TME) is a fundamental component of brain cancer pathophysiology. Glioma cells release factors that function as chemoattractants and influence the TME. Reciprocally, the activity of neurons from the surrounding TME drives the proliferation and growth of glial malignancies through paracrine signaling, brain-derived neurotrophic factor (BDNF) being a key secreted factor. BDNF binds with high affinity to the tropomyosin receptor kinase B (TrkB). Recent work from our group has shown that the TrkB.T1 splice variant is upregulated in human gliomas. In addition, TrkB.T1 overexpression enhances the tumor aggressiveness in vivo and is associated with the downregulation of genes involved in facilitating tumor cell recognition and elimination in vitro. However, the role of TrkB.T1 splice variant in this bidirectional communication between glioma cells and the surrounding cells remains unknown. Our aim was to assess if increased levels of TrkB.T1 observed in gliomas harbor a role in modulating immune responses. Thus, we explored the immune cell heterogeneity associated with increased levels of TrkB.T1 in vivo using a glioma mouse model engineered with RCAS/tv-a technology. Tumors overexpressing TrkB.T1 show decreased overall immune infiltration but increased neutrophil recruitment. Neutrophils have been associated with unfavorable prognosis in gliomas, a decrease in the tumor-infiltrating effector lymphocytes, and worst patterns of response to immunotherapy. In fact, we also observe a decrease in the CD8+ population when TrkB.T1 is overexpressed, suggesting that TrkB.T1 might support an immunosuppressive microenvironment. Thus, we next explored in vitro the communication mechanisms associated with an increase in TrkB.T1 using 3T3 cells that were transduced with pLJM1-lentivirus to overexpress TrkB.T1. These cells were serum-starved and treated with BDNF and the conditioned media was subjected to a cytokine multiplex analysis. The results show that TrkB.T1 significantly increases key chemokine levels previously described to be involved in the recruitment of neutrophils. Taken together, this work shows that the highly expressed TrkB.T1 receptor in gliomas might support an immunosuppressive microenvironment through the recruitment of neutrophils and represents a potential target for modulating glioma-immune cell interactions needed to curb disease progression, and warrants further investigation. Citation Format: Leyre Merino-Galan, Sergio Ortiz-Espinosa, Matthew Hathaway, Ashmitha Rajendran, Hawa Larissa Jagana, Gabriel Rubio, Maryam Shabar, Noemi Reche-Ley, Siobhan S Pattwell. TrkB.T1 receptor promotes an immunosuppressive microenvironment driven by neutrophil recruitment in gliomas [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B024.
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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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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; both teacher heads agree on what is shown here.
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".