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

Jean-David Fumet1,2,3, Emilie Lardenois4,5, Isabelle Ray-Coquard4,6

  • 1GINECO & Department of Medical Oncology, Center GF Leclerc, 1 rue du Professeur Marion, 21000 Dijon, France.

Cancers
|March 10, 2022
PubMed
Abstract

Insights

High intratumoral CD3+ T cells and HLA-E expression in ovarian cancer correlate with improved survival. Homologous recombination deficiency (HRD) is linked to HLA-E and better outcomes, suggesting HLA-E/CD94-NKG2A/2C as a target, especially in HRD-positive cases.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Ovarian cancer treatments using PD-1/PD-L1 inhibitors have yielded disappointing results.
  • Exploring alternative immune targets is crucial for improving patient outcomes.
  • This study investigates the tumor immune microenvironment (TME) in relation to genomic instability in high-grade serous ovarian carcinoma (HGSOC).

Purpose of the Study:

  • To characterize the TME based on genomic instability in HGSOC patients.
  • To assess the impact of genomic instability on immune cell infiltration and expression within the TME.
  • To identify potential immune targets for HGSOC treatment.

Main Methods:

  • Analysis of 103 HGSOC tumor samples from the AGO-OVAR-12 trial.
  • Comprehensive TME analysis using immunohistochemistry on tissue microarrays.
  • Evaluation of genomic instability via comparative genomic hybridization, including HRD score, genomic index, and copy number alterations.

Main Results:

  • High intratumoral CD3+ T lymphocytes were associated with longer progression-free survival (32 vs. 19.6 months) and overall survival (OS).
  • Elevated HLA-E expression on tumor cells correlated with significantly longer OS (median not reached vs. 52.9 months).
  • Homologous recombination deficiency (HRD) profile was linked to high HLA-E expression and improved OS; intratumoral CD3 and tumor cell HLA-E were key predictors in multivariate analysis.

Conclusions:

  • The study suggests HLA-E/CD94-NKG2A/2C as a potential immune target in ovarian cancer.
  • This target may be particularly relevant for the subgroup of patients with HRD-positive ovarian carcinoma.
  • Understanding the interplay between genomic instability and the TME can guide the development of novel immunotherapies.
Keywords:
HLA-EHRDcopy number alterationshomologous recombination deficiencyovarian cancertumor immune microenvironment

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