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

Journal article


Publication Details

Author(s): Goode EL, Block MS, Kalli KR, Vierkant RA, Chen W, Fogarty ZC, Gentry-Maharaj A, Toloczko A, Hein A, Bouligny AL, Jensen A, Osorio A, Hartkopf AD, Ryan A, Chudecka-Glaz A, Magliocco AM, Hartmann A, Jung AY, Gao B, Hernandez BY, Fridley BL, Mccauley BM, Kennedy CJ, Wang C, Karpinskyj C, De Sousa CB, Tiezzi DG, Wachter D, Herpel E, Taran FA, Modugno F, Nelson G, Lubinski J, Menkiszak J, Alsop J, Lester J, Garcia-Donas J, Nation J, Hung J, Palacios J, Rothstein JH, Kelley JL, De Andrade JM, Robles-Diaz L, Intermaggio MP, Widschwendter M, Beckmann M, Rübner M, Jimenez-Linan M, Singh N, Oszurek O, Harnett PR, Rambau PF, Sinn P, Wagner P, Ghatage P, Sharma R, Edwards RP, Ness RB, Orsulic S, Brucker SY, Johnatty SE, Longacre TA, Eilber U, Mcguire V, Sieh W, Natanzon Y, Li Z, Whittemore AS, Defazio A, Staebler A, Karlan BY, Gilks B, Bowtell DD, Hogdall E, Candido Dos Reis FJ, Steed H, Campbell IG, Gronwald J, Benitez J, Koziak JM, Chang-Claude J, Moysich KB, Kelemen LE, Cook LS, Goodman MT, Jose Garcia M, Fasching P, Kommoss S, Deen S, Kjaer SK, Menon U, Brenton JD, Pharoah PDP, Chenevix-Trench G, Huntsman DG, Winham SJ, Kobel M, Ramus SJ
Journal: JAMA Oncology
Publication year: 2017
Volume: 3
Journal issue: 12
ISSN: 2374-2437
eISSN: 2374-2445


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.


FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Hein, Alexander PD Dr.
Frauenklinik
Rübner, Matthias PD Dr.
Frauenklinik
Wachter, David PD Dr.
Pathologisches Institut


External institutions with authors

Addenbrooke's Hospital
Alberta Health Services (AHS)
Barts Health NHS Trust
Cedars-Sinai Medical Center
Danish Cancer Society Research Center
Deutsches Krebsforschungszentrum (DKFZ)
H. Lee Moffitt Cancer Center & Research Institute
HM Hospitales
Hospital Universitario 12 de Octubre
Icahn School of Medicine at Mount Sinai
Mayo Clinic
Medical University of South Carolina (MUSC)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Roswell Park Cancer Institute
Royal Alexandra Hospital (RAH)
Ruprecht-Karls-Universität Heidelberg
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Stanford University
Universidad de Alcalá (UAH)
Universitätsklinikum Heidelberg
Universitätsklinikum Tübingen
University College London (UCL)
University of British Columbia
University of Calgary
University of Cambridge
University of Hawaii (U.H.)
University of New Mexico
University of New South Wales (UNSW)
University of Nottingham
University of Pittsburgh
University of São Paulo / Universidade de São Paulo (USP)
University of Sydney
University of Texas Health Science Center at Houston (UTHealth)


How to cite

APA:
Goode, E.L., Block, M.S., Kalli, K.R., Vierkant, R.A., Chen, W., Fogarty, Z.C.,... Ramus, S.J. (2017). Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer. JAMA Oncology, 3(12). https://dx.doi.org/10.1001/jamaoncol.2017.3290

MLA:
Goode, Ellen L., et al. "Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer." JAMA Oncology 3.12 (2017).

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Last updated on 2019-18-07 at 07:26