Abstract 443: Prognostic significance of CXCL12 protein levels in high-grade serous ovarian carcinoma
Bibliographic record
Abstract
Abstract Signals mediated by the C-X-C chemokine ligand 12 (CXCL12; stromal-derived factor 1) and its receptor CXCR4 have been implicated in cancer progression through multiple tumorigenesis processes, including cancer cell proliferation, survival, invasion and tumor angiogenesis. In vitro and murine models recently demonstrated that this axis is also involved in the mechanism of tumor immune evasion and resistance to immune checkpoint inhibitors. In human ovarian cancer, this axis has been associated with ascites, nodes and peritoneal metastasis. We investigated the prognostic value of CXCL12 protein expression and association with CD8+ T cell infiltration in a cohort of 203 patients diagnosed with a high-grade serous ovarian carcinoma (HGSC). Quantitative immunofluorescence allowed us to evaluate the frequency and level of expression of CXCL12 and CD8+ cell density in the epithelial and stromal tumor compartments. CXCL12 expression in the epithelial tumor compartment was significantly higher than in the stromal compartment (p<0.0001). Strikingly, high levels of tumoral CXCL12 expression were significantly associated with a worse progression-free survival (PFS) and overall survival (OS) (log-rank test, p = 0.007 & p = 0.006, respectively). The Kaplan-Meier median PFS and OS were respectively of 17±1.5 and 42±6.9 months in patients with high levels and of 18±3.6 and 61±7.5 months in patients with low levels of CXCL12. Notably, multivariate analysis showed that CXCL12 levels were associated with a worse outcome independent of FIGO stage and residual disease. No correlation was observed between CXCL12 expression levels and CD8+ T cell density. Intriguingly, in CD8+ subgroup analyses, the prognostic value of CXCL12 levels was restricted to tumors with low intraepithelial CD8+ T cell densities. Flow cytometry and quantitative real-time PCR results suggest that CXCL12 promotes a mesenchymal phenotype and increased expression of cancer stem cells markers on human ovarian cancer cells. In conclusion, modulation of the CXCL12/CXCR4 axis is a promising approach in HGSC that may potentiate immunotherapies and may act on epithelial-to-mesenchymal transition. Our study highlights the rationale to evaluate in the clinical setting treatments targeting the CXCL12/CXCR4 in HGSC, specifically in patients lacking CD8+ T cell tumor infiltration. Citation Format: Laurence Buisseret, Vincent Delisle, Laudine Communal, Sandra Pommey, John Stagg. Prognostic significance of CXCL12 protein levels in high-grade serous ovarian carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 443.
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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 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".