Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages
BackgroundFor 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1307873/full |
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| author | Sarah Nersesian Sarah Nersesian Riley J. Arseneau Riley J. Arseneau Jorge P. Mejia Jorge P. Mejia Stacey N. Lee Stacey N. Lee Lauren P. Westhaver Nigel W. Griffiths Stephanie R. Grantham Liliane Meunier Laudine Communal Avik Mukherjee Anne-Marie Mes-Masson Anne-Marie Mes-Masson Thomas Arnason Thomas Arnason Brad H. Nelson Brad H. Nelson Brad H. Nelson Jeanette E. Boudreau Jeanette E. Boudreau Jeanette E. Boudreau |
| author_facet | Sarah Nersesian Sarah Nersesian Riley J. Arseneau Riley J. Arseneau Jorge P. Mejia Jorge P. Mejia Stacey N. Lee Stacey N. Lee Lauren P. Westhaver Nigel W. Griffiths Stephanie R. Grantham Liliane Meunier Laudine Communal Avik Mukherjee Anne-Marie Mes-Masson Anne-Marie Mes-Masson Thomas Arnason Thomas Arnason Brad H. Nelson Brad H. Nelson Brad H. Nelson Jeanette E. Boudreau Jeanette E. Boudreau Jeanette E. Boudreau |
| author_sort | Sarah Nersesian |
| collection | DOAJ |
| description | BackgroundFor 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.MethodsWe 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.ResultsWe 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 infiltration of CD16a+ cells, and their co-localization with macrophages, T cells, NK cells, in one of six cellular neighborhoods that we defined with our spatial assessment.ConclusionsImmune cell neighborhoods containing CD16a+ cells are associated with improved OS and PFS for patients with HGSC. Patterns of immunologic neighborhoods differentiate patient outcomes, and could inform future, more precise approaches to treatment. |
| first_indexed | 2024-03-08T12:30:01Z |
| format | Article |
| id | doaj.art-391fa1616f8d4b798e9dc94b54faccbb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T12:30:01Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-391fa1616f8d4b798e9dc94b54faccbb2024-01-22T04:25:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.13078731307873Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophagesSarah Nersesian0Sarah Nersesian1Riley J. Arseneau2Riley J. Arseneau3Jorge P. Mejia4Jorge P. Mejia5Stacey N. Lee6Stacey N. Lee7Lauren P. Westhaver8Nigel W. Griffiths9Stephanie R. Grantham10Liliane Meunier11Laudine Communal12Avik Mukherjee13Anne-Marie Mes-Masson14Anne-Marie Mes-Masson15Thomas Arnason16Thomas Arnason17Brad H. Nelson18Brad H. Nelson19Brad H. Nelson20Jeanette E. Boudreau21Jeanette E. Boudreau22Jeanette E. Boudreau23Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaBeatrice Hunter Cancer Research Institute, Halifax, NS, CanadaBeatrice Hunter Cancer Research Institute, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaBeatrice Hunter Cancer Research Institute, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaBeatrice Hunter Cancer Research Institute, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaBeatrice Hunter Cancer Research Institute, Halifax, NS, CanadaCentre de recherche du Centre hospitalier de l’Université de Montréal and Institut du cancer de Montréal, Montreal, QC, CanadaCentre de recherche du Centre hospitalier de l’Université de Montréal and Institut du cancer de Montréal, Montreal, QC, CanadaAkoya Biosciences, Menlo Park, CA, United StatesCentre de recherche du Centre hospitalier de l’Université de Montréal and Institut du cancer de Montréal, Montreal, QC, CanadaDepartment of Medicine, Université de Montréal, Montreal, QC, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology & Laboratory Medicine, QEII Health Sciences Centre, Nova Scotia Health (Central Zone), Halifax, NS, CanadaDeeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada0Department of Medical Genetics, University of British Columbia, Vancouver, BC, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaBeatrice Hunter Cancer Research Institute, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaBackgroundFor 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.MethodsWe 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.ResultsWe 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 infiltration of CD16a+ cells, and their co-localization with macrophages, T cells, NK cells, in one of six cellular neighborhoods that we defined with our spatial assessment.ConclusionsImmune cell neighborhoods containing CD16a+ cells are associated with improved OS and PFS for patients with HGSC. Patterns of immunologic neighborhoods differentiate patient outcomes, and could inform future, more precise approaches to treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1307873/fullnatural killer (NK) cellovarian cancerhigh grade serous cancerspatial biologyCD16A |
| spellingShingle | Sarah Nersesian Sarah Nersesian Riley J. Arseneau Riley J. Arseneau Jorge P. Mejia Jorge P. Mejia Stacey N. Lee Stacey N. Lee Lauren P. Westhaver Nigel W. Griffiths Stephanie R. Grantham Liliane Meunier Laudine Communal Avik Mukherjee Anne-Marie Mes-Masson Anne-Marie Mes-Masson Thomas Arnason Thomas Arnason Brad H. Nelson Brad H. Nelson Brad H. Nelson Jeanette E. Boudreau Jeanette E. Boudreau Jeanette E. Boudreau Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages Frontiers in Immunology natural killer (NK) cell ovarian cancer high grade serous cancer spatial biology CD16A |
| title | Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages |
| title_full | Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages |
| title_fullStr | Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages |
| title_full_unstemmed | Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages |
| title_short | Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages |
| title_sort | improved overall survival in patients with high grade serous ovarian cancer is associated with cd16a immunologic neighborhoods containing nk cells t cells and macrophages |
| topic | natural killer (NK) cell ovarian cancer high grade serous cancer spatial biology CD16A |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1307873/full |
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