Cancers (Feb 2022)
Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial
- 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,
- Jérôme Alexandre,
- Aurélie Houlier,
- Jalid Sehouli,
- Emilie Sohier,
- Rainer Kimmig,
- Bertrand Dubois,
- Dominique Spaeth,
- Isabelle Treilleux,
- Jean-Sébastien Frenel,
- Uwe Herwig,
- Olivia Le Saux,
- Nathalie Bendriss-Vermare,
- Andreas du Bois
Affiliations
- Jean-David Fumet
- GINECO & Department of Medical Oncology, Center GF Leclerc, 1 rue du Professeur Marion, 21000 Dijon, France
- Emilie Lardenois
- Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Immune Surveillance and Therapeutic Targeting” Team, 69000 Lyon, France
- Isabelle Ray-Coquard
- Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Immune Surveillance and Therapeutic Targeting” Team, 69000 Lyon, France
- Philipp Harter
- AGO & Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, 45136 Essen, Germany
- Florence Joly
- GINECO & Department of Medical Oncology, Baclesse Cancer Center, 14118 Caen, France
- Ulrich Canzler
- AGO & Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany & National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
- Caroline Truntzer
- Platform of Transfer in Cancer Biology, 21079 Dijon, France
- Olivier Tredan
- GINECO & Medical Oncology Department, Centre Léon Bérard, 28, rue Laennec, Université Claude Bernard Lyon 1, 69008 Lyon, France
- Clemens Liebrich
- AGO & Klinikum Wolfsburg, amO—Interdisziplinäres ambulantes Onkologiezentrum am Klieversberg, Sauerbruchstrasse 7, 38840 Wolfsburg, Germany
- Alain Lortholary
- GINECO & Confluent Private Hospital, Institut de Cancérologie Catherine de Sienne, 44200 Nantes, France
- Daniel Pissaloux
- Leon Berard Center, Department of Pathology, 69000 Lyon, France
- Alexandra Leary
- GINECO & Medical Oncology Department, Institut Gustave Roussy, 94805 Villejuif, France
- Jacobus Pfisterer
- AGO & Zentrum für Gynäkologische Onkologie, Herzog-Friedrich-Str. 21, 24103 Kiel, Germany
- Alexandre Eeckhoutte
- INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.m) PSL Research University, Institut Curie, 75005 Paris, France
- Felix Hilpert
- AGO & Krankenhaus Jerusalem, Moorkamp 2-6, Onkologische Tagesklinik, 20357 Hamburg, Germany
- Michel Fabbro
- GINECO & ICM Val d’Aurelle, oncologie médicale, 208, Avenue des Apothicaires, 34298 Montpellier, France
- Christophe Caux
- Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Immune Surveillance and Therapeutic Targeting” Team, 69000 Lyon, France
- Jérôme Alexandre
- GINECO & Medical Oncology Department, Hopital Cochin, 75014 Paris, France
- Aurélie Houlier
- Leon Berard Center, Department of Pathology, 69000 Lyon, France
- Jalid Sehouli
- AGO & Charité, Medical University of Berlin, Department of Gynecology with Center of Oncological Surgery, Augustenburger Platz 1, 13353 Berlin, Germany
- Emilie Sohier
- Synergie Lyon Cancer, Bio-Informatics Platform, 69000 Lyon, France
- Rainer Kimmig
- AGO & West-German Cancer Center, Department of Gynecology and Obstetrics, University of Duisburg-Essen Germany, 45136 Essen, Germany
- Bertrand Dubois
- Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Immune Surveillance and Therapeutic Targeting” Team, 69000 Lyon, France
- Dominique Spaeth
- GINECO & Medical Oncology Department Centre d’Oncologie de Gentilly, 54000 Nancy, France
- Isabelle Treilleux
- Leon Berard Center, Department of Pathology, 69000 Lyon, France
- Jean-Sébastien Frenel
- GINECO & Medical Oncology Department Institut de cancerologie de l’Ouest site René Gauducheau, 44800 Saint Herblain, France
- Uwe Herwig
- AGO & Albertinen-Krankenhaus, Department Gynecology, Süntelstraße 11a, 22457 Hamburg, Germany
- Olivia Le Saux
- Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Immune Surveillance and Therapeutic Targeting” Team, 69000 Lyon, France
- Nathalie Bendriss-Vermare
- Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Immune Surveillance and Therapeutic Targeting” Team, 69000 Lyon, France
- Andreas du Bois
- AGO & Evangelische Kliniken Essen Mitte (KEM), 45136 Essen, Germany
- DOI
- https://doi.org/10.3390/cancers14051189
- Journal volume & issue
-
Vol. 14,
no. 5
p. 1189
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.
Keywords
- ovarian cancer
- tumor immune microenvironment
- HLA-E
- copy number alterations
- homologous recombination deficiency
- HRD