Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2022

Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial

Isabelle Ray-Coquard
Philipp Harter
  • Fonction : Auteur
Ulrich Canzler
  • Fonction : Auteur
Caroline Truntzer
Clemens Liebrich
  • Fonction : Auteur
Alain Lortholary
  • Fonction : Auteur
Daniel Pissaloux
  • Fonction : Auteur
Alexandra Leary
  • Fonction : Auteur
Jacobus Pfisterer
  • Fonction : Auteur
Alexandre Eeckhoutte
  • Fonction : Auteur
  • PersonId : 1083874
  • IdRef : 271060999
Felix Hilpert
  • Fonction : Auteur
Michel Fabbro
Jérôme Alexandre
  • Fonction : Auteur
Jalid Sehouli
  • Fonction : Auteur
Emilie Sohier
  • Fonction : Auteur
Rainer Kimmig
  • Fonction : Auteur
Dominique Spaeth
  • Fonction : Auteur
Jean-Sébastien Frenel
Uwe Herwig
  • Fonction : Auteur
Andreas Du Bois

Résumé

Background: Following disappointing results with PD-1/PD-L1 inhibitors in ovarian cancer, it is essential to explore other immune targets. The aim of this study is to describe the tumor immune microenvironment (TME) according to genomic instability in high grade serous ovarian carcinoma (HGSOC) patients receiving primary debulking surgery followed by carboplatin-paclitaxel chemotherapy +/− nintedanib. Methods: 103 HGSOC patients’ tumor samples from phase III AGO-OVAR-12 were analyzed. A comprehensive analysis of the TME was performed by immunohistochemistry on tissue microarray. Comparative genomic hybridization was carried out to evaluate genomic instability signatures through homologous recombination deficiency (HRD) score, genomic index, and somatic copy number alterations. The relationship between genomic instability and TME was explored. Results: Patients with high intratumoral CD3+ T lymphocytes had longer progression-free survival (32 vs. 19.6 months, p = 0.009) and overall survival (OS) (median not reached). High HLA-E expression on tumor cells was associated with a longer OS (median OS not reached vs. 52.9 months, p = 0.002). HRD profile was associated with high HLA-E expression on tumor cells and an improved OS. In the multivariate analysis, residual tumor, intratumoral CD3, and HLA-E on tumor cells were more predictive than other parameters. Conclusions: Our results suggest HLA-E/CD94-NKG2A/2C is a potential immune target particularly in the HRD positive ovarian carcinoma subgroup.
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hal-03769697 , version 1 (27-02-2024)

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Jean-David Fumet, Emilie Lardenois, Isabelle Ray-Coquard, Philipp Harter, Florence Joly, et al.. Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial. Cancers, 2022, 14 (5), pp.1189. ⟨10.3390/cancers14051189⟩. ⟨hal-03769697⟩
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