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876 T cell exhaustion correlates with homologous recombination and determines survival in high grade serous ovarian cancer
  1. Mathilde Del1,
  2. Anna Salvioni2,
  3. Guillaume Bataillon1,
  4. Marie Michelas2,
  5. Bertille Segier1,
  6. Sarah Betrian1,
  7. Gwenaël Ferron1,
  8. Maha Ayyoub2 and
  9. Alejandra Martinez1
  1. 1Institut Claudius Regaud, Toulouse, France
  2. 2INSERM, Toulouse, France


Introduction/Background Homologous recombination deficiency (HRD) exhibit distinct immune characteristics compared to HR Proficient (HRP) ovarian cancers. Tumor infiltrating lymphocytes (TILs) are enriched in HRD tumors, both through innate and adaptive immune mechanisms. However, there are mechanisms for evading immune recognition in the HRD group, and there is a subset of HRP tumors with enhanced CD8 T cell response and better survival. It is likely that T cell infiltration alone may not be sufficient to characterize tumor immunogenicity in both HRD and HRP tumors.

The study aims to explore how genetic anomalies contribute to modulate immunophenotype and T cell composition in high grade serous ovarian cancer (HGSOC).

Methodology HR status was analyzed using myChoice CDx Plus (Myriad genetics). Immune microenvironement was assessed by multiplex immunofluorescence of FFPE tumor samples to assess infiltration by CD4 and CD8 T cells, immunophenotype, PD-L1 expression and multiparametric flow cytometry of frozen viable cell suspensions to assess CD4 and CD8 phenotype including differentiation status and T-cell exhaustion.

Results The study included 43 patients with HRD and 37 patients with HRD, stage III-IV, ovarian cancer. Infiltration of T cells (measured as CD3/mm2) was similar, regardless of HRD status, both within the intraepithelial and the stromal area. There were no difference in PD-L1 expression or in immune phenotype according to genetic results, with excluded phenotype being the most frequent. Interestingly, a significantly higher abundance of intraepithelial T cells was observed in BRCAmut tumors, compared to HRD BRCAwt tumors. Phenotype analysis of CD8 and CD4 T cells showed an increased frequency of terminally exhausted T cells (expressing PD-1 and TIM-3, CD39) in HRD tumors, without any difference between BRCAmut and BRCAwt tumors. T cell exhaustion correlated with PFS in multivariable analyses.

Conclusion These results demonstrate an association between T-cell exhaustion and HRD. T-cell exhaustion is an independent predictor of disease outcome in HGSOC.

Disclosures No discosures to report.

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