Evidence map›Paper›PMID 29049607›Full record

ArticleJAMA oncology2017

Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

Ovarian Tumor Tissue Analysis (OTTA) Consortium, Ellen L Goode, Matthew S Block, Kimberly R Kalli, Robert A Vierkant, Wenqian Chen, Zachary C Fogarty, Aleksandra Gentry-Maharaj, Aleksandra Tołoczko, Alexander Hein and 90 more

2 registry-linked trialsOpen access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in JAMA oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 277 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
277citing papers in PubMed, 3 pooled it
16.2field-weighted citation impact, top 1% 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.

NCT03922776 naterminatednot on this mapstarted 2019, after this paper: background citation

Phenotypic Characterization Tumor-infiltrating Lymphocytes at Diagnosis and After Chemotherapy in Advanced High-grade Serous Ovarian Cancer in Blood, Ascites, Peritoneal Biopsy

TypeinterventionalSponsorCentre Oscar LambretRan2019 to 2024Enrolled36ConditionsOvarian Cancer Stage IIIC, Fallopian Tube Cancer Stage IIIC, Fallopian Tube Cancer Stage IV, Ovarian Cancer Stage IVArmsBlood sample collection
NCT06084195 narecruitingnot on this mapstarted 2023, after this paper: background citation

Unravelling Tumour Biology In Ovarian Cancer With Precision Imaging

TypeinterventionalSponsorInstitut du Cancer de Montpellier - Val d'AurelleRan2023 to 2029Enrolled120ConditionsHigh Grade Serous Ovarian CancerArmsBlood sample and tissue sample
3 · Its place in the literature

Who cites it

277 citing papers in PubMed, 3 syntheses or guidelines pooled it, 391 citations in OpenAlex.

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217 more citing papers are in PubMed but not listed here.

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

100 authors at 20 institutions in 11 countries.

Ovarian Tumor Tissue Analysis (OTTA) Consortium
Ellen L GoodeDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Matthew S BlockDepartment of Medical Oncology, Mayo Clinic, Rochester, MN, USA
Kimberly R KalliDepartment of Medical Oncology, Mayo Clinic, Rochester, MN, USA
Robert A VierkantDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Wenqian ChenDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
Zachary C FogartyDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Aleksandra Gentry-MaharajGynaecological Cancer Research Centre, Department of Women’s Cancer, Institute for Women’s Health, University College London, London, UK
Aleksandra TołoczkoInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Alexander HeinDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg Comprehensive Cancer Center, Erlangen EMN, Germany
Aliecia L BoulignyDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Allan JensenVirus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Ana OsorioHuman Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Andreas HartkopfTübingen University Hospital, Department of Women’s Health, Tübingen, Germany
Andy RyanGynaecological Cancer Research Centre, Department of Women’s Cancer, Institute for Women’s Health, University College London, London, UK
Anita Chudecka-GłazDepartment of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland
Anthony M MaglioccoDepartment of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA
Arndt HartmannInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University
Audrey Y JungDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Bo GaoCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
Brenda Y HernandezCancer Center, University of Hawaii, Honolulu, HI, USA
Brooke L FridleyDepartment of Biostatistics and Bioinformatics, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA
Bryan M McCauleyDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Catherine J KennedyCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
Chen WangDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Chloe KarpinskyjGynaecological Cancer Research Centre, Department of Women’s Cancer, Institute for Women’s Health, University College London, London, UK
Christiani B de SousaDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Daniel G TiezziDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
David L WachterInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University
Esther HerpelTissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Germany and Institute of Pathology, University of Heidelberg, Heidelberg, Germany
Florin Andrei TaranTübingen University Hospital, Department of Women’s Health, Tübingen, Germany
Francesmary ModugnoDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Gregg NelsonDepartment of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Jan LubińskiInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Janusz MenkiszakDepartment of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland
Jennifer AlsopDepartment of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
Jenny LesterWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Jesús García-DonasMedical Oncology Service, HM Hospitales – Centro Integral Oncológico HM Clara Campal, Madrid, Spain
Jill NationDepartment of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Jillian HungCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
José PalaciosPathology Department, Hospital Universitario Ramón y Cajal. IRYCIS. Universidad de Alcalá, Madrid, Spain. CIBERONC
Joseph H RothsteinDepartment of Population Health Science and Policy, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Joseph L KelleyDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Jurandyr M de AndradeDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Luis Robles-DíazFamilial Cancer Unit and Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
Maria P IntermaggioSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia
Martin WidschwendterGynaecological Cancer Research Centre, Department of Women’s Cancer, Institute for Women’s Health, University College London, London, UK
Matthias W BeckmannDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg Comprehensive Cancer Center, Erlangen EMN, Germany
Matthias RuebnerDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg Comprehensive Cancer Center, Erlangen EMN, Germany
Mercedes Jimenez-LinanDepartment of Histopathology, Addenbrookes Hospital, Cambridge, UK
Naveena SinghDepartment of Pathology, Barts Health National Health Service Trust, London, UK
Oleg OszurekInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Paul R HarnettCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
Peter F RambauDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
Peter SinnDepartment of Pathology, Institute of Pathology, Heidelberg University Hospital, Germany
Philipp WagnerTübingen University Hospital, Department of Women’s Health, Tübingen, Germany
Prafull GhatageDepartment of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Raghwa SharmaPathology West ICPMR Westmead, Westmead Hospital, The University of Sydney, Sydney, Australia
Robert P EdwardsDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Roberta B NessThe University of Texas School of Public Health, Houston, TX, USA
Sandra OrsulicWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Sara Y BruckerTübingen University Hospital, Department of Women’s Health, Tübingen, Germany
Sharon E JohnattyDepartment of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Teri A LongacreDepartment of Pathology, Stanford University, Stanford, CA, USA
Eilber UrsulaDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Valerie McGuireDepartment of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA
Weiva SiehDepartment of Population Health Science and Policy, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Yanina NatanzonDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Zheng LiDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Alice S WhittemoreDepartment of Health Research and Policy, Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA
deFazio AnnaCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
Annette StaeblerTübingen University Hospital, Institute of Pathology, Tübingen, Germany
Beth Y KarlanWomen’s Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Blake GilksGenetic Pathology Evaluation Centre, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia,Canada
David D BowtellCancer Genomics Program, Research Department, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Estrid HøgdallVirus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Francisco J Candido dos ReisDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Helen SteedDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, Alberta, Canada
Ian G CampbellCancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia
Jacek GronwaldInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Javier BenítezHuman Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Jennifer M KoziakAlberta Health Services-Cancer Care, Calgary, Alberta, Canada
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Kirsten B MoysichDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Linda E KelemenDepartment of Public Health Sciences, Medical University of South Carolina and Hollings Cancer Center, Charleston, SC, USA
Linda S CookDivision of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM, USA
Marc T GoodmanSamuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
María José GarcíaHuman Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Peter A FaschingDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg Comprehensive Cancer Center, Erlangen EMN, Germany
Stefan KommossTübingen University Hospital, Department of Women’s Health, Tübingen, Germany
Suha DeenDepartment of Histopathology, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
Susanne K KjaerVirus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Usha MenonGynaecological Cancer Research Centre, Department of Women’s Cancer, Institute for Women’s Health, University College London, London, UK
James D BrentonDepartment of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK
Paul DP PharoahDepartment of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
Georgia Chenevix-TrenchDepartment of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia
David G HuntsmanDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Stacey J WinhamDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Martin KöbelDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
Susan J RamusSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia
Mayo Clinic in Florida · USUniversity Children's Hospital Tübingen · DEUniversity of Calgary · CACedars-Sinai Medical Center · USUniversidade de São Paulo · BRInternational Hereditary Cancer Center · PLPomeranian Medical University · PLStanford University · USUniversitätsklinikum Erlangen · DEUniversity College London · GBUniversity of Pittsburgh · USWestmead Hospital · AUBreast Cancer Now · GBCentre for Biomedical Network Research on Rare Diseases · ESComprehensive Cancer Center Erlangen · DEDanish Cancer Society · DKGerman Cancer Research Center · DEIcahn School of Medicine at Mount Sinai · USMayo Clinic · USMoffitt Cancer Center · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
WITHIN SUBJ VARIABILITY IN MEASUREMENTS DRUG METABOL ENZYMES IN HLTY SUBJM01RR000056 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEVINE, ARTHUR S · 1985 to 2006
$29.2M
Northern California Cooperative Family Registry for Breast CancerU01CA069417 · NCI · NORTHERN CALIFORNIA CANCER CENTER · PI JOHN, ESTHER M. · 1995 to 2010
$22.4M
RPCI-UPCI Ovarian Cancer SPOREP50CA159981 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B. · 2013 to 2025
$19.6M
Mayo Cancer Genetic Epidemiology Training ProgramR25CA092049 · NCI · MAYO CLINIC ROCHESTER · PI PETERSEN, GLORIA M., VACHON, CELINE M · 2001 to 2018
$5.3M
Novel immunological biomarkers ovarian cancer prognosisR01CA188900 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B., SEGAL, BRAHM H. · 2015 to 2019
$3.3M
Inflammation and Ovarian CancerR01CA095023 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BUNKER, CLAREANN H. · 2003 to 2008
$2.7M
Genetic Variation in the NF-kappaB Pathway and Ovarian Cancer EtiologyR01CA122443 · NCI · MAYO CLINIC ROCHESTER · PI GOODE, ELLEN L. · 2007 to 2012
$2.7M
Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 16561NCATS NIH HHS UL1 TR000124NCI NIH HHS K07 CA080668NCI NIH HHS K07 CA143047NCI NIH HHS P30 CA016056NCI NIH HHS P30 CA138313NCI NIH HHS P50 CA136393NCI NIH HHS P50 CA159981NCI NIH HHS R01 CA095023NCI NIH HHS R01 CA122443NCI NIH HHS R01 CA160669NCI NIH HHS R01 CA188900NCI NIH HHS R25 CA092049NCI NIH HHS U01 CA069417NCRR NIH HHS M01 RR000056
6 · The paper itself

Abstract

Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Exposures: Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcomes and Measures: Overall survival time. Results: The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form. Conclusions and Relevance: This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

Indexed as

BRCA2 ProteinCarcinoma, Ovarian EpithelialCD8 AntigensCohort StudiesCystadenocarcinoma, SerousFemaleHumansLymphocytes, Tumor-InfiltratingMiddle AgedMutationNeoplasm GradingOvarian NeoplasmsProspective StudiesSurvival AnalysisTreatment OutcomeBRCA2 ProteinBRCA2 protein, humanCD8 Antigens

Identifiers

PMID29049607
PMCPMC5744673
OpenAlexW2765953690

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Registered trials

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.