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

卵巢癌中基因组不稳定性由特定肿瘤微环境定义:AGO OVAR 12 试验的亚组分析

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作者:Jean-David Fumet, Emilie Lardenois, Isabelle Ray-Coquard, Philipp Harter, Florence Joly, Ulrich Canzler, Caroline Truntzer, Olivier Tredan, Clemens Liebrich, Alain Lortholary, Daniel Pissaloux, Alexandra Leary, Jacobus Pfisterer, Alexandre Eeckhoutte, Felix Hilpert, Michel Fabbro, Christophe Caux, J

Background

Following disappointing

Conclusions

Our results suggest HLA-E/CD94-NKG2A/2C is a potential immune target particularly in the HRD positive ovarian carcinoma subgroup.

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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