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1286 Multimodal characterisation of the tumour microenvironment of high grade serous ovarian cancer
  1. Kate Glennon1,
  2. Donagh Egan2,
  3. Myriam Nabhan2,
  4. Walter Koch2,
  5. Ann Treacy2 and
  6. Donal Brennan1,2
  1. 1Mater Misericordiae Univeristy Hospital, Dublin, Ireland
  2. 2University Hospital Dublin, Dublin, Ireland


Introduction/Background We present a multimodal characterisation of the tumour microenvironment (TME) of primary and metastatic high grade serous ovarian cancer (HGSOC) samples using immunohistochemistry (IHC) and proteonomic analysis.

Methodology IHC was performed on 24 H&E tumour samples from seven patients. The scanned images were annotated to assess intra-epithelial and stromal CD4 and CD8 expression using ImageScope and analysed using the Aperio Nuclear Algorithm v9. Proteomic analysis was conducted on the IHC slides. Enriched pathways were identified using Gene Set Enrichment Analysis (GSEA) pathways using a False Discovery Rate (FDR) <0.25 as statistically significant.

Results An IHC analysis revealed that in the majority of primary ovarian samples (5/7, 71.4%) a higher density of CD8+ stromal TILs (sTILs) compared to intraepithelial (iTILs) was evident (median sTILs 381 (SD±335) cells/mm2 versus median iTILs 200 (±299) cells/mm2 (p=0.8).

In IHC from 4/6 different metastatic sites (omentum, vagina, spleen and peritoneum) the density of CD8+ sTILs was higher than iTILs, demonstrating these tumours were immune excluded.

This correlates with the proteomic analysis. The pathway enrichment analysis illustrates an upregulation of the adaptive immune system and mhc2 presentation pathways in the metastatic samples, suggesting an immune-mediated differences between primary and metastatic HGSOC. In addition, L1 cell-adhesion molecule (L1CAM) expression appears to be associated with metastasis suggesting its expression is associated with progression of disease.

Conclusion Our results demonstrate an immune mediated difference between the stroma and intraepithelial tumour sites and between primary and metastatic HGSOC. HGSOC samples were ‘cold’ or immune excluded. Further investigation into understanding whether immune cells are exhausted or, impeded from entering the tumour from the stroma may be key to furthering the understanding of the biology of anti-tumour immunity in ovarian cancer.

Disclosures n/a.

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