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

Page DB 1 , Broeckx G 2 , Jahangir CA 3 , Verbandt S 4 , Gupta RR 5 , Thagaard J 6 Show all authors , Khiroya R 7 , Kos Z 8 , Abduljabbar K 9 , Acosta Haab G 10 , Acs B 11 , Akturk G 12 , Almeida JS 13 , Alvarado-Cabrero I 14 , Azmoudeh-Ardalan F 15 , Badve S 16 , Baharun NB 17 , Bellolio ER 18 , Bheemaraju V 19 , Blenman KR 20 , Botinelly Mendonça Fujimoto L 21 , Bouchmaa N 22 , Burgues O 23 , Cheang MCU 24 , Ciompi F 25 , Cooper LA 26 , Coosemans A 27 , Corredor G 28 , Dantas Portela FL 29 , Deman F 2 , Demaria S 30 , Dudgeon SN 31 , Elghazawy M 32 , Ely S 33 , Fernandez-Martín C 34 , Fineberg S 35 , Fox SB 36 , Gallagher WM 3 , Giltnane JM 37 , Gnjatic S 38 , Gonzalez-Ericsson PI 39 , Grigoriadis A 40 , Halama N 41 , Hanna MG 42 , Harbhajanka A 43 , Hardas A 44 , Hart SN 45 , Hartman J 46 , Hewitt S 47 , Hida AI 48 , Horlings HM 49 , Husain Z 50 , Hytopoulos E 51 , Irshad S 52 , Janssen EA 53 , Kahila M 54 , Kataoka TR 55 , Kawaguchi K 56 , Kharidehal D 19 , Khramtsov AI 57 , Kiraz U 53 , Kirtani P 58 , Kodach LL 59 , Korski K 60 , Kovács A 61 , Laenkholm AV 62 , Lang-Schwarz C 63 , Larsimont D 64 , Lennerz JK 65 , Lerousseau M 66 , Li X 67 , Ly A 68 , Madabhushi A 69 , Maley SK 70 , Manur Narasimhamurthy V 71 , Marks DK 72 , McDonald ES 73 , Mehrotra R 74 , Michiels S 75 , Minhas FUAA 76 , Mittal S 77 , Moore DA 78 , Mushtaq S 79 , Nighat H 80 , Papathomas T 81 , Penault-Llorca F 82 , Perera RD 83 , Pinard CJ 84 , Pinto-Cardenas JC 85 , Pruneri G 86 , Pusztai L 87 , Rahman A 3 , Rajpoot NM 88 , Rapoport BL 89 , Rau TT 90 , Reis-Filho JS 91 , Ribeiro JM 92 , Rimm D 54 , Vincent-Salomon A 93 , Salto-Tellez M 94 , Saltz J 95 , Sayed S 96 , Siziopikou KP 97 , Sotiriou C 98 , Stenzinger A 99 , Sughayer MA 100 , Sur D 101 , Symmans F 102 , Tanaka S 103 , Taxter T 104 , Tejpar S 4 , Teuwen J 105 , Thompson EA 106 , Tramm T 107 , Tran WT 108 , van der Laak J 109 , van Diest PJ 110 , Verghese GE 40 , Viale G 111 , Vieth M 63 , Wahab N 112 , Walter T 66 , Waumans Y 113 , Wen HY 42 , Yang W 114 , Yuan Y 115 , Adams S 72 , Bartlett JMS 116 , Loibl S 117 , Denkert C 118 , Savas P 119 , Loi S 119 , Salgado R 2 , Specht Stovgaard E 120

Affiliations 

  • 1 Earle A Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
  • 2 Department of Pathology, GZA-ZNA Hospitals, Antwerp, Belgium
  • 3 UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
  • 4 Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
  • 5 Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA
  • 6 Technical University of Denmark, Kongens Lyngby, Denmark
  • 7 Department of Cellular Pathology, University College Hospital, London, UK
  • 8 Department of Pathology and Laboratory Medicine, BC Cancer Vancouver Centre, University of British Columbia, Vancouver, BC, Canada
  • 9 Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK
  • 10 Hospital Maria Curie, Buenos Aires, Argentina
  • 11 Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
  • 12 Translational Molecular Biomarkers, Merck & Co Inc, Kenilworth, NJ, USA
  • 13 National Cancer Institute, Division of Cancer Epidemiology and Genetics (DCEG), Rockville, MD, USA
  • 14 Oncology Hospital, Star Medica Centro, Mexico
  • 15 Tehran University of Medical Sciences, Tehran, Iran
  • 16 Pathology and Laboratory Medicine, Emory University School of Medicine, Emory University Winship Cancer Institute, Atlanta, GA, USA
  • 17 The National University of Malaysia, Kuala Lumpur, Malaysia
  • 18 Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile
  • 19 Department of Pathology, Narayana Medical College, Nellore, India
  • 20 Internal Medicine Section of Medical Oncology and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA
  • 21 Amazonas Federal University, Manaus, Brazil
  • 22 Institute of Biological Sciences, Faculty of Medical Sciences, Mohammed VI Polytechnic University (UM6P), Ben-Guerir, Morocco
  • 23 Pathology Department, Hospital Cliníco Universitario de Valencia/Incliva, Valencia, Spain
  • 24 Head of Integrative Genomics Analysis in Clinical Trials, ICR-CTSU, Division of Clinical Studies, Institute of Cancer Research, London, UK
  • 25 Radboud University Medical Center, Department of Pathology, Nijmegen, The Netherlands
  • 26 Department of Pathology, Northwestern Feinberg School of Medicine, Chicago, IL, USA
  • 27 Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, KU Leuven, Leuven, Belgium
  • 28 Biomedical Engineering Department, Emory University, Atlanta, GA, USA
  • 29 Hospital Universitário Getúlio Vargas, Manaus, Brazil
  • 30 Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
  • 31 Conputational Biology and Bioinformatics, Yale University, New Haven, CT, USA
  • 32 University of Surrey, Guildford, UK
  • 33 Translational Pathology, Translational Sciences and Diagnostics/Translational Medicine/R&D, Bristol Myers Squibb, Princeton, NJ, USA
  • 34 Instituto Universitario de Investigación en Tecnología Centrada en el Ser Humano, HUMAN-tech, Universitat Politècnica de València, Valencia, Spain
  • 35 Montefiore Medical Center and the Albert Einstein College of Medicine, New York, NY, USA
  • 36 Department of Pathology, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  • 37 Genentech, South San Francisco, CA, USA
  • 38 Department of Oncological Sciences, Medicine Hem/Onc, and Pathology, Tisch Cancer Institute - Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • 39 Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
  • 40 Cancer Bioinformatics, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
  • 41 Translational Immunotherapy, German Cancer Research Center, Heidelberg, Germany
  • 42 Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • 43 Case Western University, Cleveland, OH, USA
  • 44 Pathobiology & Population Sciences, The Royal Veterinary College, London, UK
  • 45 Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • 46 Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden
  • 47 Department of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
  • 48 Department of Pathology, Matsuyama Shimin Hospital, Matsuyama, Japan
  • 49 Division of Pathology, Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands
  • 50 Praava Health, Dhaka, Bangladesh
  • 51 iRhythm Technologies Inc., San Francisco, CA, USA
  • 52 King's College London & Guy's & St Thomas' NHS Trust, London, UK
  • 53 Department of Pathology, Stavanger University Hospital, Stavanger, Norway
  • 54 Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
  • 55 Department of Pathology, Iwate Medical University, Iwate, Japan
  • 56 Department of Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • 57 Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
  • 58 Department of Histopathology, Aakash Healthcare Super Speciality Hospital, New Delhi, India
  • 59 Department of Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
  • 60 Data, Analytics and Imaging, Product Development, F.Hoffmann-La Roche AG, Basel, Switzerland
  • 61 Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 62 Surgical Pathology, Zealand University Hospital, Roskilde, Denmark
  • 63 Institute of Pathology, Klinikum Bayreuth GmbH, Friedrich-Alexander-University Erlangen-Nuremberg, Bayreuth, Germany
  • 64 Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
  • 65 Center for Integrated Diagnostics, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
  • 66 Centre for Computational Biology (CBIO), Mines Paris, PSL University, Paris, France
  • 67 Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
  • 68 Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
  • 69 Biomedical Engineering, Radiology and Imaging Sciences, Biomedical Informatics, Pathology, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
  • 70 NRG Oncology/NSABP Foundation, Pittsburgh, PA, USA
  • 71 Manipal Hospitals, Bangalore, India
  • 72 Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA
  • 73 Breast Cancer Translational Research Group, University of Pennsylvania, Philadelphia, PA, USA
  • 74 Indian Cancer Genome Atlas, Pune, India
  • 75 Office of Biostatistics and Epidemiology, Gustave Roussy, Oncostat U1018, Inserm, University Paris-Saclay, Ligue Contre le Cancer labeled Team, Villejuif, France
  • 76 Tissue Image Analytics Centre, Warwick Cancer Research Centre, PathLAKE Consortium, Department of Computer Science, University of Warwick, Coventry, UK
  • 77 Department of Chemical Engineering, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
  • 78 CRUK Lung Cancer Centre of Excellence, UCLH, London, UK
  • 79 Department of Biochemistry, Ziauddin University, Karachi, Pakistan
  • 80 Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Raipur, India
  • 81 Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
  • 82 Centre Jean Perrin, INSERM U1240, Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, Clermont-Ferrand, France
  • 83 School of Electrical, Mechanical and Infrastructure Engineering, University of Melbourne, Melbourne, VIC, Australia
  • 84 Radiogenomics Laboratory, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  • 85 Diagnostico de Salud Animal SA, Ciudad de México, Mexico
  • 86 Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 87 Yale Cancer Center, New Haven, CT, USA
  • 88 University of Warwick, Warwick, UK
  • 89 The Medical Oncology Centre of Rosebank, Johannesburg, South Africa
  • 90 Institute of Pathology, University Hospital Düsseldorf and Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
  • 91 Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • 92 Département de Médecine Oncologique, Institute Gustave Roussy, Villejuif, France
  • 93 Department of Diagnostic and Theranostic Medicine, Institut Curie, University Paris-Sciences et Lettres, Paris, France
  • 94 Integrated Pathology Unit, Institute of Cancer Research, London, UK
  • 95 Department of Biomedical Informatics, Stony Brook Medicine, New York, NY, USA
  • 96 Department of Pathology, Aga Khan University, Nairobi, Kenya
  • 97 Department of Pathology, Section of Breast Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 98 Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium
  • 99 Institute of Pathology, University Hospital Heidelberg, Centers for Personalized Medicine (ZPM), Heidelberg, Germany
  • 100 King Hussein Cancer Center, Amman, Jordan
  • 101 Department of Medical Oncology, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
  • 102 University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 103 Kyoto University, Kyoto, Japan
  • 104 Tempus Labs, Chicago, IL, USA
  • 105 AI for Oncology Lab, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 106 Mayo Clinic, Jacksonville, FL, USA
  • 107 Pathology, and Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
  • 108 Department of Radiation Oncology, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  • 109 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
  • 110 Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
  • 111 Department of Pathology, European Institute of Oncology & University of Milan, Milan, Italy
  • 112 Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, Coventry, UK
  • 113 CellCarta NV, Antwerp, Belgium
  • 114 Fudan Medical University Shanghai Cancer Center, Shanghai, PR China
  • 115 Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 116 University of Edinburgh, Edinburgh, UK
  • 117 Department of Medicine and Research, German Breast Group, Neu-Isenburg, Germany
  • 118 Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum Marburg, Marburg, Germany
  • 119 Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  • 120 Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark
J Pathol, 2023 Aug;260(5):514-532.
PMID: 37608771 DOI: 10.1002/path.6165

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. © 2023 The Pathological Society of Great Britain and Ireland.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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