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Spatial analyses of immune cell infiltration in cancer: current methods and future directions. A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

  • David B. Page
  • , Glenn Broeckx
  • , Chowdhury Arif Jahangir
  • , Sara Verbandt
  • , Rajarsi R. Gupta
  • , Jeppe Thagaard
  • , Reena Khiroya
  • , Zuzana Kos
  • , Khalid Abduljabbar
  • , Gabriela Acosta Haab
  • , Balazs Acs
  • , Guray Akturk
  • , Jonas S. Almeida
  • , Isabel Alvarado-Cabrero
  • , Farid Azmoudeh-Ardalan
  • , Sunil Badve
  • , Nurkhairul Bariyah Baharun
  • , Enrique R. Bellolio
  • , Vydehi Bheemaraju
  • , Kim R.M. Blenman
  • Luciana Botinelly Mendonça Fujimoto, Najat Bouchmaa, Octavio Burgues, Maggie Chon U. Cheang, Francesco Ciompi, Lee A.D. Cooper, An Coosemans, Germán Corredor, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Sarah N. Dudgeon, Mahmoud Elghazawy, Scott Ely, Claudio Fernandez-Martín, Susan Fineberg, Stephen B. Fox, William M. Gallagher, Jennifer M. Giltnane, Sacha Gnjatic, Paula I. Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G. Hanna, Aparna Harbhajanka, Alexandros Hardas, Steven N. Hart, Johan Hartman, Stephen Hewitt, Akira I. Hida, Hugo M. Horlings, Zaheed Husain, Evangelos Hytopoulos, Sheeba Irshad, Emiel A.M. Janssen, Mohamed Kahila, Tatsuki R. Kataoka, Kosuke Kawaguchi, Durga Kharidehal, Andrey I. Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L. Kodach, Konstanty Korski, Anikó Kovács, Anne Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K. Lennerz, Marvin Lerousseau, Xiaoxian Li, Amy Ly, Anant Madabhushi, Sai K. Maley, Vidya Manur Narasimhamurthy, Douglas K. Marks, Elizabeth S. McDonald, Ravi Mehrotra, Stefan Michiels, Fayyaz ul Amir Afsar Minhas, Shachi Mittal, David A. Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D. Perera, Christopher J. Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Arman Rahman, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T. Rau, Jorge S. Reis-Filho, Joana M. Ribeiro, David Rimm, Anne Vincent-Salomon, Manuel Salto-Tellez, Joel Saltz, Shahin Sayed, Kalliopi P. Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A. Sughayer, Daniel Sur, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E. Aubrey Thompson, Trine Tramm, William T. Tran, Jeroen van der Laak, Paul J. van Diest, Gregory E. Verghese, Giuseppe Viale, Michael Vieth, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y. Wen, Wentao Yang, Yinyin Yuan, Sylvia Adams, John Mark Seaverns Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Roberto Salgado, Elisabeth Specht Stovgaard
  • Providence Cancer Institute
  • GZA-ZNA Hospitals
  • University of Antwerp
  • University College Dublin
  • KU Leuven
  • Technical University of Denmark
  • Visiopharm
  • University College Hospital
  • University of British Columbia
  • The Institute of Cancer Research
  • Hospital de Oncología Maria Curie
  • Karolinska Institutet
  • Merck
  • National Institutes of Health
  • Instituto Mexicano del Seguro Social
  • Tehran University of Medical Sciences
  • Emory University
  • Universiti Kebangsaan Malaysia
  • Universidad de la Frontera
  • Narayana Medical College & Hospital
  • Yale University
  • Amazonas Federal University
  • Mohammed VI Polytechnic University
  • Hospital Clinico Universitario de Valencia
  • Radboud University Nijmegen
  • Northwestern University
  • Emory University
  • Hospital Universitário Getúlio Vargas
  • Cornell University
  • University of Surrey
  • Ain Shams University
  • Bristol-Myers Squibb
  • Polytechnic University of Valencia
  • Albert Einstein College of Medicine
  • University of Melbourne
  • Genentech, Inc
  • Icahn School of Medicine at Mount Sinai
  • Vanderbilt University
  • King's College London
  • German Cancer Research Center
  • Memorial Sloan-Kettering Cancer Center
  • Case Western Reserve University
  • Royal Veterinary College University of London
  • Mayo Clinic Rochester, MN
  • Matsuyama Shimin Hospital
  • Netherlands Cancer Institute
  • Praava Health
  • iRhythm Technologies Inc.
  • Guy's and St Thomas' NHS Foundation Trust
  • Stavanger University Hospital
  • University of Stavanger
  • Iwate Medical University
  • Kyoto University
  • Children's Memorial Hospital
  • Aakash Healthcare Super Speciality Hospital
  • Antoni van Leeuwenhoek Hospital
  • F. Hoffmann-La Roche AG
  • Sahlgrenska University Hospital
  • University of Gothenburg
  • Sjællands Universitetshospital
  • University of Copenhagen
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Université libre de Bruxelles
  • Massachusetts General Hospital
  • Mines ParisTech
  • Institut Curie
  • INSERM U900
  • Georgia Institute of Technology
  • NSABP Foundation, Inc.
  • Manipal Academy of Higher Education
  • New York University
  • University of Pennsylvania
  • Indian Cancer Genomic Atlas
  • Innovation and Policy Foundation
  • University of Paris Sud
  • University of Warwick
  • University of Washington
  • CRUK Lung Cancer Centre of Excellence
  • Ziauddin University
  • All India Institute of Medical Sciences, Raipur
  • University of Birmingham
  • Université Clermont Auvergne
  • Peter Maccallum Cancer Centre
  • University of Toronto
  • University of Guelph
  • Lakeshore Animal Health Partners
  • Diagnostico de Salud Animal SA
  • IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
  • University of Milan
  • The Medical Oncology Centre of Rosebank
  • University of Pretoria
  • Heinrich Heine University Düsseldorf
  • Queen's University Belfast
  • Aga Khan University
  • Heidelberg University 
  • King Hussein Cancer Center
  • Iuliu Hatieganu University of Medicine and Pharmacy
  • University of Texas MD Anderson Cancer Center
  • Tempus Labs, Inc.
  • Mayo Clinic in Jacksonville, Florida
  • Aarhus University
  • Utrecht University
  • Johns Hopkins University
  • IRCCS Istituto Europeo di Oncologia - Milano
  • CellCarta
  • Fudan University
  • University of Edinburgh
  • German Breast Group
  • University of Marburg

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers.

Original languageEnglish
Pages (from-to)514-532
Number of pages19
JournalJournal of Pathology
Volume260
Issue number5
DOIs
StatePublished - Aug 2023

Keywords

  • Immunoscore
  • TIL
  • multispectral immunofluorescence
  • sTIL score
  • spatial heterogeneity
  • spatial statistics
  • tumor infiltrating lymphocytes

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