Evidence map›Paper›PMID 36368129›Full record

ArticleGynecologic oncology2023

Profiling the immune landscape in mucinous ovarian carcinoma.

Nicola S Meagher, Phineas Hamilton, Katy Milne, Shelby Thornton, Bronwyn Harris, Ashley Weir, Jennifer Alsop, Christiani Bisinoto, James D Brenton, Angela Brooks-Wilson and 35 more

Open access · hybridAbstract read
In one paragraph

Article in Gynecologic oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 25 citations in OpenAlex.

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  12. The Role ofInternational journal of women's health · 2025
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  18. Immune checkpoint inhibitors in ovarian cancer: where do we go from here?Cancer drug resistance (Alhambra, Calif.) · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors at 20 institutions in 8 countries.

Nicola S MeagherSchool of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia; The Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council New South Wales, Australia. Electronic address: nicola.meagher@sydney.edu.au.
Phineas HamiltonTrev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada.
Katy MilneTrev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada.
Shelby ThorntonTrev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada.
Bronwyn HarrisTrev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada.
Ashley WeirSchool of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Jennifer AlsopCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Christiani BisinotoDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
James D BrentonCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Angela Brooks-WilsonCanada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
Derek S ChiuBritish Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada.
Kara L Cushing-HaugenProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Sian FeredayPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Dale W GarsedPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Simon A GaytherCenter for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Aleksandra Gentry-MaharajMRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
Blake GilksDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Mercedes Jimenez-LinanDepartment of Histopathology, Addenbrooke's Hospital, Cambridge, UK.
Catherine J KennedyCentre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia.
Nhu D LeCancer Control Research, BC Cancer, Vancouver, BC, Canada.
Anna M PiskorzCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Marjorie J RigganDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
Mitul ShahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Naveena SinghDepartment of Pathology, Barts Health National Health Service Trust, London, UK; Department of Anatomical Pathology, Vancouver General Hospital, Vancouver, Canada.
Aline TalhoukBritish Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Martin WidschwendterEUTOPS Institute, University of Innsbruck, Innsbruck, Austria.
David D L BowtellPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Francisco J Candido Dos ReisDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Linda S CookEpidemiology, School of Public Health, University of Colorado, Aurora, CO, USA; Community Health Sciences, University of Calgary, Calgary, AB, Canada.
Renée T FortnerDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
María J GarcíaComputational Oncology Group, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Holly R HarrisProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
David G HuntsmanDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada.
Anthony N KarnezisDepartment of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA, USA.
Martin KöbelDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
Usha MenonMRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
Paul D P PharoahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Jennifer A DohertyHuntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
Michael S AnglesioBritish Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Malcolm C PikeDepartment of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Population Health and Public Health Sciences, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Celeste Leigh PearceDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Michael L FriedlanderSchool of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Sydney, New South Wales, Australia; Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, New South Wales, Australia.
Anna DeFazioThe Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council New South Wales, Australia; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia.
Brad H NelsonTrev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada.
Susan J RamusSchool of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia. Electronic address: s.ramus@unsw.edu.au.
BC Cancer Agency · CAUniversity of Cambridge · GBUNSW Sydney · AUThe University of Melbourne · AUUniversity of British Columbia · CAUniversidade de São Paulo · BRVancouver General Hospital · CAWestmead Institute for Medical Research · AUAddenbrooke's Hospital · GBBarts Health NHS Trust · GBCanada's Michael Smith Genome Sciences Centre · CACedars-Sinai Medical Center · USColorado School of Public Health · USDuke Medical Center · USFred Hutch Cancer Center · USHeidelberg University · DEHuntsman Cancer Institute · USMemorial Sloan Kettering Cancer Center · USMRC Clinical Trials Unit at UCL · GBSpanish National Cancer Research Centre · ES

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Epidemiology of Ovarian Cancer:New HypothesesR01CA087538 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSSING, MARY ANNE · 2002 to 2006
$3.5M
Steroid Hormone Genes and Ovarian Cancer RiskR01CA112523 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSSING, MARY ANNE · 2006 to 2010
$3.3M
Epidemiologic factors and survival by molecular subtypes of ovarian cancerR01CA168758 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DOHERTY, JENNIFER A., ROSSING, MARY ANNE · 2013 to 2016
$2.6M
Mitochondrial DNA and Ovarian Cancer Risk and SurvivalR01CA160669 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI COOK, LINDA S · 2012 to 2016
$2.2M
Cancer Research UK 15601Cancer Research UK 22905Cancer Research UK A15601Cancer Research UK A17197Cancer Research UK A22905Cancer Research UK C490/A16561Department of HealthMedical Research Council MC_UU_00004/01NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA087538NCI NIH HHS R01 CA112523NCI NIH HHS R01 CA160669NCI NIH HHS R01 CA168758
6 · The paper itself

Abstract

objectiveMucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients.

methodsWe performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration.

resultsMean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates.

conclusionIn summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.

Indexed as

B7-H1 AntigenOvarian NeoplasmsCarcinoma, Ovarian EpithelialCD8-Positive T-LymphocytesFemaleForkhead Transcription FactorsHumansLymphocytes, Tumor-InfiltratingTumor MicroenvironmentB7-H1 AntigenForkhead Transcription FactorsImmune infiltrateMucinous ovarian carcinomaRare histotype

Identifiers

PMID36368129
PMCPMC10374276
OpenAlexW4308544300

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.