P08.06.B THE EGFL7-INTEGRIN Β2 AXIS: A NOVEL REGULATOR OF IMMUNE EVASION IN GLIOBLASTOMA
Bibliographic record
Abstract
Abstract BACKGROUND Glioblastoma is the most aggressive form of malignant brain cancer, characterized by an immunosuppressive environment that leads to immune evasion. Multiple strategies have been undertaken to shift the immune landscape within the glioma microenvironment (GME) to an anti-tumorigenic state, with little success. Thus, immune evasion remains a major roadblock in developing effective glioma therapies. Epidermal growth factor-like protein 7 (EGFL7), an angiogenic factor, highly expressed in the GME, has been implicated in promoting immune escape in breast and lung cancer, however its immunomodulatory function remains unclear in glioblastoma. In the current study, we investigated the role of EGFL7 in shaping the immune microenvironment in glioblastoma and identified a key underlying mechanism driving immune evasion. MATERIAL AND METHODS Using gain-of-function and loss-of-function murine glioblastoma models, we investigated the influence of EGFL7 on the immune system within the GME. After 4 weeks of tumor growth, immune cells from tumor tissues were isolated for single-cell RNA sequencing (scRNA-seq) and we integrated spatial transcriptomics, to determine their spatial distribution. Flow cytometry and immunohistochemistry were employed for validation, respectively. Co-immunoprecipitation and mass spectrometry analysis identified EGFL7 interaction partners in the GME. Functional studies using migration and T cell suppression assays employing purified EGFL7 were undertaken. Therapeutic intervention tested on tumor bearing mice. RESULTS ScRNA-seq analysis of immune cells from murine GME revealed that EGFL7 promotes an immunosuppressive microenvironment characterized by increased infiltration of anti-inflammatory macrophages and myeloid-derived suppressor cells. Moreover, EGFL7 expression was associated with increased T cell exhaustion within the lymphoid compartment. In contrast, the knockout of EGFL7 led to reversal of the immunosuppressive phenotype. Mass spectrometry analysis of the EGFL7 interactome identified integrin β2, a key immune cell receptor, as a novel binding partner. Mechanistic studies revealed that EGFL7-integrin β2 interaction modulates immune cell migration and alters the immune landscape in glioblastoma, thereby influencing the survival of tumor bearing mice. CONCLUSION Our study uncovers that the interaction of EGFL7 with integrin β2 plays a critical role in driving immunosuppression in glioblastoma and identifies EGFL7-integrin β2 axis as a viable target for therapeutic intervention for reversing immune dysfunction in glioblastoma.
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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.014 | 0.006 |
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".