Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

Sep 22, 2026

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Improved overall survival in high-grade serous ovarian cancer is linked to specific immune microenvironments. The study addresses longstanding stagnation in outcomes despite tumor mutations and immune-cell infiltration and the limited benefit of existing immunotherapies. Using duplicate tumor core samples from 939 patients, researchers applied high-parameter immunohistochemistry/Opal multiplex, digital pathology, computational biology, and multivariate analysis to map immune cell subsets and spatial neighborhoods, identifying CD16a+ neighborhood patterns associated with better overall and progression-free survival.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Background

Methods

Results

Conclusions

Introduction

TYPE Original Research PUBLISHED 22 January 2024 DOI 10.3389/fimmu.2023.1307873 OPEN ACCESS EDITED BY AJ Robert McGray, University at Buffalo, United States REVIEWED BY Mark Long, University at Buffalo, United States Sieghart Sopper, Innsbruck Medical University, Austria *CORRESPONDENCE Jeanette E. Boudreau [jeanette.boudreau@dal.ca](jeanette.boudreau@dal.ca) RECEIVED 05 October 2023 ACCEPTED 22 December 2023 PUBLISHED 22 January 2024 CITATION Nersesian S, Arseneau RJ, Mejia JP, Lee SN, Westhaver LP, Grifﬁths NW, Grantham SR, Meunier L, Communal L, Mukherjee A, Mes-Masson A-M, Arnason T, Nelson BH and Boudreau JE (2024) Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages. Front. Immunol. 14:1307873 . doi: 10.3389/fimmu.2023.1307873 COPYRIGHT © 2024 Nersesian, Arseneau, Mejia, Lee, Westhaver, Grifﬁths, Grantham, Meunier, Communal, Mukherjee, Mes-Masson, Arnason, Nelson and Boudreau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Improved overall survival inpatients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages Sarah Nersesian 1,2, Riley J. Arseneau 2,3, Jorge P. Mejia 1,2, Stacey N. Lee 1,2, Lauren P. Westhaver 3, Nigel W. Grifﬁths3, Stephanie R. Grantham 2, Liliane Meunier 4, Laudine Communal 4, Avik Mukherjee 5, Anne-Marie Mes-Masson 4,6, Thomas Arnason 3,7, Brad H. Nelson 8,9,10 and Jeanette E. Boudreau 1,2,3* 1 Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada, 2 Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada, 3 Department of Pathology, Dalhousie University, Halifax, NS, Canada, 4Centre de recherche du Centre hospitalier de l’ Universite´ de Montre´al and Institut du cancer de Montre´al, Montreal, QC, Canada, 5Akoya Biosciences, Menlo Park, CA, United States, 6 Department of Medicine, Universite´ de Montre´al, Montreal, QC, Canada, 7 Department of Pathology & Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, Canada, 8 Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada, 9 Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada, 10 Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Background: For patients with high grade serous carcinoma of the ovary (HGSC), survival rates have remained static for the last half century. Despite the presence of tumor mutations and inﬁltration of immune cells, existing immunotherapies have achieved little success against HGSC. These observations highlight a gap in the understanding of how the immune system functions and interacts within HGSC tumors. Methods: We analyzed duplicate core samples from 939 patients with HGSC to understand patterns of immune cell inﬁltration, localization, and associations with clinical features. We used high-parameter immunohistochemical/Opal multiplex, digital pathology, computational biology, and multivariate analysis to identify immune cell subsets and their associations with HGSC tumors. Results: We deﬁned six patterns of cellular inﬁltration by spatially restricted unsupervised clustering of cell subsets. Each pattern was represented to some extent in most patient samples, but their speciﬁc distributions differed. Overall (OS) and progression-free survival (PFS) corresponded with higher inﬁltra

FAQs

What main factor is associated with improved survival in high-grade serous ovarian cancer patients?

Improved overall and progression-free survival corresponds to higher infiltration of CD16a+ cells and their co-localization with macrophages, T cells, and NK cells within defined immune cell neighborhoods.

How were immune cell patterns and neighborhoods identified in the study?

The study analyzed duplicate core samples from 939 patients and used high-parameter immunohistochemistry/Opal multiplex, digital pathology, computational biology, and multivariate analysis to define immune cell subsets and spatially restricted clusters.

Why do the authors emphasize the need for better immune understanding in HGSC?

Despite immune infiltration and intermediate neoantigen load, anti-PD-L1 therapies have been largely ineffective, and survival rates have remained static, indicating a gap in understanding how immune system interactions function within HGSC tumors.

Sep 22, 2026

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