Abstract 6167: Defining the role of transcriptional coregulator MED15 in immune adaptation in cancer
Bibliographic record
Abstract
Abstract The immune system is widely recognized as an important regulator of cancer progression and metastasis, where immune cells can actively promote or inhibit tumor growth. Initially, immune cells act to eradicate cells with emerging cancerous properties, but cancer cells reprogram these immune cells to instead help promote growth of the cancer. Modulating the immune system is therefore an important approach in cancer therapy, however, the identification of new molecular targets is still needed. A potential target includes MED15, a subunit of the transcriptional coregulator complex Mediator, which interacts with transcription factors (TFs) bound to gene regulatory elements. MED15 upregulation occurs in several cancers and is associated with aggressive clinical presentation and shorter patient survival. The precise role that MED15 plays in immune responses in cancer, however, is not known. To investigate this, MED15KO A549 lung adenocarcinoma cells were used to analyze the expression and secretion of various pro-inflammatory immune response genes. The MED15KO cells displayed downregulated expression of the immune genes CXCL3, CXCL5, and PTGS2, and the immune receptor TLR4, indicated by qPCR. Decreased expression of the pro-inflammatory modulator COX2 (the product of PTGS2) was also observed using immunoblot analysis and decreased secretion of CXCL chemokines and PGE2 (the proinflammatory mediator synthesized by COX2) was observed using ELISA and multiplex assays. The functional effects resulting from this lower expression/secretion of pro-inflammatory mediators were examined, specifically the migration of immune cells towards the cancer cells. A decrease in the migration of THP-1 differentiated macrophages was observed towards the MED15KO cells in comparison to WT A549 cells, using a transwell migration assay. To determine how MED15 regulates the expression/secretion of these pro-inflammatory genes a Cut&Run protocol was optimized. This will reveal if MED15 binds chromatin near TFs known to regulate these immune genes, identifying candidate TFs that may cooperate with MED15. In sum, this data suggests that MED15 is required for the expression and secretion of these immune genes and their ligands, while highlighting an important role for MED15 in pro-inflammatory immune responses in cancer. Citation Format: Sara Cristiano, Xuanjin Cheng, Stefan Taubert. Defining the role of transcriptional coregulator MED15 in immune adaptation in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6167.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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; 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".