Scientific article
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Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma

Published inNature communications, vol. 15, no. 1, 5932
Publication date2024-07-16
First online date2024-07-16
Abstract

PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8+ PD-1+ T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.93 (95% CI 0.85-1.00) and iii) high CD8B/FOXP3 and high CD8B/ENTPD1 ratios are significantly associated with positive response to NACT + P, while KDR and VEGFR2 expression are associated with resistance. These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2+ endothelial cells, could overcome immune resistance of ovarian cancers.

Keywords
  • Humans
  • Female
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Neoadjuvant Therapy / methods
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Forkhead Transcription Factors / metabolism
  • Forkhead Transcription Factors / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Tumor Microenvironment / immunology
  • Tumor Microenvironment / drug effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Neoplasm Grading
  • B7-H1 Antigen / metabolism
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / antagonists & inhibitors
  • Immunotherapy / methods
Funding
  • Fondation ARC pour la Recherche sur le Cancer (ARC Foundation for Cancer Research) [PGA1 RC20170205307]
Citation (ISO format)
LE SAUX, Olivia et al. Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma. In: Nature communications, 2024, vol. 15, n° 1, p. 5932. doi: 10.1038/s41467-024-47000-5
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Identifiers
Additional URL for this publicationhttps://www.nature.com/articles/s41467-024-47000-5
Journal ISSN2041-1723
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