Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial - Archive ouverte HAL Access content directly
Journal Articles Cancers Year : 2022

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

Philipp Harter
  • Function : Author
Ulrich Canzler
  • Function : Author
Caroline Truntzer
Clemens Liebrich
  • Function : Author
Alain Lortholary
  • Function : Author
Daniel Pissaloux
  • Function : Author
Alexandra Leary
  • Function : Author
Jacobus Pfisterer
  • Function : Author
Alexandre Eeckhoutte
  • Function : Author
Felix Hilpert
  • Function : Author
Michel Fabbro
Christophe Caux
  • Function : Author
Jérôme Alexandre
  • Function : Author
Jalid Sehouli
  • Function : Author
Emilie Sohier
  • Function : Author
Rainer Kimmig
  • Function : Author
Dominique Spaeth
  • Function : Author
Jean-Sébastien Frenel
Uwe Herwig
  • Function : Author
Andreas Du Bois

Abstract

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.

Dates and versions

hal-03769697 , version 1 (05-09-2022)

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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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