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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 Publisher Pubmed



Page DB1 ; Broeckx G2, 3 ; Jahangir CA4 ; Verbandt S5 ; Gupta RR6 ; Thagaard J7, 8 ; Khiroya R9 ; Kos Z10 ; Abduljabbar K11 ; Acosta Haab G12 ; Acs B13, 14 ; Akturk G15 ; Almeida JS16 ; Alvaradocabrero I17 Show All Authors
Authors
  1. Page DB1
  2. Broeckx G2, 3
  3. Jahangir CA4
  4. Verbandt S5
  5. Gupta RR6
  6. Thagaard J7, 8
  7. Khiroya R9
  8. Kos Z10
  9. Abduljabbar K11
  10. Acosta Haab G12
  11. Acs B13, 14
  12. Akturk G15
  13. Almeida JS16
  14. Alvaradocabrero I17
  15. Azmoudehardalan F18
  16. Badve S19
  17. Baharun NB20
  18. Bellolio ER21
  19. Bheemaraju V22
  20. Blenman KRM23, 24
  21. Botinelly Mendonca Fujimoto L25
  22. Bouchmaa N26
  23. Burgues O27
  24. Cheang MCU28
  25. Ciompi F29
  26. Cooper LAD30
  27. Coosemans A31
  28. Corredor G32
  29. Dantas Portela FL33
  30. Deman F2
  31. Demaria S34, 35
  32. Dudgeon SN36
  33. Elghazawy M37, 38
  34. Ely S39
  35. Fernandezmartin C40
  36. Fineberg S41
  37. Fox SB42
  38. Gallagher WM4
  39. Giltnane JM43
  40. Gnjatic S44
  41. Gonzalezericsson PI45
  42. Grigoriadis A46, 47
  43. Halama N48
  44. Hanna MG49
  45. Harbhajanka A50
  46. Hardas A51
  47. Hart SN52
  48. Hartman J14, 53
  49. Hewitt S54
  50. Hida AI55
  51. Horlings HM56
  52. Husain Z57
  53. Hytopoulos E58
  54. Irshad S59
  55. Janssen EAM60, 61
  56. Kahila M62
  57. Kataoka TR63
  58. Kawaguchi K64
  59. Kharidehal D22
  60. Khramtsov AI65
  61. Kiraz U60, 61
  62. Kirtani P66
  63. Kodach LL67
  64. Korski K68
  65. Kovacs A69, 70
  66. Laenkholm AV71, 72
  67. Langschwarz C73
  68. Larsimont D74
  69. Lennerz JK75
  70. Lerousseau M76, 77, 78
  71. Li X79
  72. Ly A80
  73. Madabhushi A81
  74. Maley SK82
  75. Manur Narasimhamurthy V83
  76. Marks DK84
  77. Mcdonald ES85
  78. Mehrotra R86, 87
  79. Michiels S88
  80. Minhas FUAA89
  81. Mittal S90
  82. Moore DA91
  83. Mushtaq S92
  84. Nighat H93
  85. Papathomas T94, 95
  86. Penaultllorca F96
  87. Perera RD97, 98
  88. Pinard CJ99, 100, 101, 102
  89. Pintocardenas JC103
  90. Pruneri G104, 105
  91. Pusztai L106, 107
  92. Rahman A4
  93. Rajpoot NM108
  94. Rapoport BL109, 110
  95. Rau TT111
  96. Reisfilho JS112
  97. Ribeiro JM113
  98. Rimm D62, 114
  99. Vincentsalomon A115
  100. Saltotellez M116, 117
  101. Saltz J118
  102. Sayed S119
  103. Siziopikou KP120
  104. Sotiriou C121, 122
  105. Stenzinger A123
  106. Sughayer MA124
  107. Sur D125
  108. Symmans F126
  109. Tanaka S127
  110. Taxter T128
  111. Tejpar S5
  112. Teuwen J129
  113. Thompson EA130
  114. Tramm T131
  115. Tran WT132
  116. Van Der Laak J133
  117. Van Diest PJ134, 135
  118. Verghese GE46, 47
  119. Viale G136
  120. Vieth M73
  121. Wahab N137
  122. Walter T76, 77, 78
  123. Waumans Y138
  124. Wen HY49
  125. Yang W139
  126. Yuan Y140
  127. Adams S84, 141
  128. Bartlett JMS142
  129. Loibl S143
  130. Denkert C144
  131. Savas P98, 145
  132. Loi S98, 146
  133. Salgado R2, 98
  134. Specht Stovgaard E147, 148
Show Affiliations
Authors Affiliations
  1. 1. Earle A Chiles Research Institute, Providence Cancer Institute, Portland, OR, United States
  2. 2. Department of Pathology, GZA-ZNA Hospitals, Antwerp, Belgium
  3. 3. Centre for Oncological Research (CORE), MIPPRO, Faculty of Medicine, Antwerp University, Antwerp, Belgium
  4. 4. UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
  5. 5. Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
  6. 6. Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, United States
  7. 7. Technical University of Denmark, Kongens Lyngby, Denmark
  8. 8. Visiopharm A/S, Horsholm, Denmark
  9. 9. Department of Cellular Pathology, University College Hospital, London, United Kingdom
  10. 10. Department of Pathology and Laboratory Medicine, BC Cancer Vancouver Centre, University of British Columbia, Vancouver, BC, Canada
  11. 11. Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom
  12. 12. Hospital Maria Curie, Buenos Aires, Argentina
  13. 13. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
  14. 14. Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden
  15. 15. Translational Molecular Biomarkers, Merck & Co Inc, Kenilworth, NJ, United States
  16. 16. National Cancer Institute, Division of Cancer Epidemiology and Genetics (DCEG), Rockville, MD, United States
  17. 17. Oncology Hospital, Star Medica Centro, Mexico
  18. 18. Tehran University of Medical Sciences, Tehran, Iran
  19. 19. Pathology and Laboratory Medicine, Emory University School of Medicine, Emory University Winship Cancer Institute, Atlanta, GA, United States
  20. 20. The National University of Malaysia, Kuala Lumpur, Malaysia
  21. 21. Departamento de Anatomia Patologica, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile
  22. 22. Department of Pathology, Narayana Medical College, Nellore, India
  23. 23. Internal Medicine Section of Medical Oncology and Yale Cancer Center, Yale School of Medicine, New Haven, CT, United States
  24. 24. Computer Science, Yale School of Engineering and Applied Science, New Haven, CT, United States
  25. 25. Amazonas Federal University, Manaus, Brazil
  26. 26. Institute of Biological Sciences, Faculty of Medical Sciences, Mohammed VI Polytechnic University (UM6P), Ben-Guerir, Morocco
  27. 27. Pathology Department, Hospital Clinico Universitario de Valencia/Incliva, Valencia, Spain
  28. 28. Head of Integrative Genomics Analysis in Clinical Trials, ICR-CTSU, Division of Clinical Studies, Institute of Cancer Research, London, United Kingdom
  29. 29. Radboud University Medical Center, Department of Pathology, Nijmegen, Netherlands
  30. 30. Department of Pathology, Northwestern Feinberg School of Medicine, Chicago, IL, United States
  31. 31. Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, KU Leuven, Leuven, Belgium
  32. 32. Biomedical Engineering Department, Emory University, Atlanta, GA, United States
  33. 33. Hospital Universitario Getulio Vargas, Manaus, Brazil
  34. 34. Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, United States
  35. 35. Department of Pathology, Weill Cornell Medicine, New York, NY, United States
  36. 36. Conputational Biology and Bioinformatics, Yale University, New Haven, CT, United States
  37. 37. University of Surrey, Guildford, United Kingdom
  38. 38. Ain Shams University, Cairo, Egypt
  39. 39. Translational Pathology, Translational Sciences and Diagnostics/Translational Medicine/R&D, Bristol Myers Squibb, Princeton, NJ, United States
  40. 40. Instituto Universitario de Investigacion en Tecnologia Centrada en el Ser Humano, HUMAN-tech, Universitat Politecnica de Valencia, Valencia, Spain
  41. 41. Montefiore Medical Center and the Albert Einstein College of Medicine, New York, NY, United States
  42. 42. Department of Pathology, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  43. 43. Genentech, South San Francisco, CA, United States
  44. 44. 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, United States
  45. 45. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  46. 46. Cancer Bioinformatics, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
  47. 47. Breast Cancer Now Research Unit, School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
  48. 48. Translational Immunotherapy, German Cancer Research Center, Heidelberg, Germany
  49. 49. Memorial Sloan Kettering Cancer Center, New York, NY, United States
  50. 50. Case Western University, Cleveland, OH, United States
  51. 51. Pathobiology & Population Sciences, The Royal Veterinary College, London, United Kingdom
  52. 52. Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
  53. 53. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
  54. 54. Department of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
  55. 55. Department of Pathology, Matsuyama Shimin Hospital, Matsuyama, Japan
  56. 56. Division of Pathology, Netherlands Cancer Institute (NKI), Amsterdam, Netherlands
  57. 57. Praava Health, Dhaka, Bangladesh
  58. 58. iRhythm Technologies Inc., San Francisco, CA, United States
  59. 59. King's College London & Guy's & St Thomas’ NHS Trust, London, United Kingdom
  60. 60. Department of Pathology, Stavanger University Hospital, Stavanger, Norway
  61. 61. Department of Chemistry, Bioscience and Environmental Technology, University of Stavanger, Stavanger, Norway
  62. 62. Department of Pathology, Yale University School of Medicine, New Haven, CT, United States
  63. 63. Department of Pathology, Iwate Medical University, Iwate, Japan
  64. 64. Department of Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
  65. 65. Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States
  66. 66. Department of Histopathology, Aakash Healthcare Super Speciality Hospital, New Delhi, India
  67. 67. Department of Pathology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
  68. 68. Data, Analytics and Imaging, Product Development, F.Hoffmann-La Roche AG, Basel, Switzerland
  69. 69. Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
  70. 70. Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  71. 71. Surgical Pathology, Zealand University Hospital, Roskilde, Denmark
  72. 72. Surgical Pathology, University of Copenhagen, Copenhagen, Denmark
  73. 73. Institute of Pathology, Klinikum Bayreuth GmbH, Friedrich-Alexander-University Erlangen-Nuremberg, Bayreuth, Germany
  74. 74. Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  75. 75. Center for Integrated Diagnostics, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States
  76. 76. Centre for Computational Biology (CBIO), Mines Paris, PSL University, Paris, France
  77. 77. Institut Curie, PSL University, Paris, France
  78. 78. INSERM, U900, Paris, France
  79. 79. Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States
  80. 80. Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
  81. 81. Biomedical Engineering, Radiology and Imaging Sciences, Biomedical Informatics, Pathology, Georgia Institute of Technology and Emory University, Atlanta, GA, United States
  82. 82. NRG Oncology/NSABP Foundation, Pittsburgh, PA, United States
  83. 83. Manipal Hospitals, Bangalore, India
  84. 84. Perlmutter Cancer Center, NYU Langone Health, New York, NY, United States
  85. 85. Breast Cancer Translational Research Group, University of Pennsylvania, Philadelphia, PA, United States
  86. 86. Indian Cancer Genome Atlas, Pune, India
  87. 87. Centre for Health, Innovation and Policy Foundation, Noida, India
  88. 88. Office of Biostatistics and Epidemiology, Gustave Roussy, Oncostat U1018, Inserm, University Paris-Saclay, Ligue Contre le Cancer labeled Team, Villejuif, France
  89. 89. Tissue Image Analytics Centre, Warwick Cancer Research Centre, PathLAKE Consortium, Department of Computer Science, University of Warwick, Coventry, United Kingdom
  90. 90. Department of Chemical Engineering, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States
  91. 91. CRUK Lung Cancer Centre of Excellence, UCLH, London, United Kingdom
  92. 92. Department of Biochemistry, Ziauddin University, Karachi, Pakistan
  93. 93. Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Raipur, India
  94. 94. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom
  95. 95. Department of Clinical Pathology, Drammen Sykehus, Vestre Viken HF, Drammen, Norway
  96. 96. Centre Jean Perrin, INSERM U1240, Imagerie Moleculaire et Strategies Theranostiques, Universite Clermont Auvergne, Clermont-Ferrand, France
  97. 97. School of Electrical, Mechanical and Infrastructure Engineering, University of Melbourne, Melbourne, VIC, Australia
  98. 98. Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  99. 99. Radiogenomics Laboratory, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  100. 100. Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
  101. 101. Department of Oncology, Lakeshore Animal Health Partners, Mississauga, ON, Canada
  102. 102. Centre for Advancing Responsible and Ethical Artificial Intelligence (CARE-AI), University of Guelph, Guelph, ON, Canada
  103. 103. Diagnostico de Salud Animal SA, Ciudad de Mexico, Mexico
  104. 104. Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  105. 105. Faculty of Medicine and Surgery, University of Milan, Milan, Italy
  106. 106. Yale Cancer Center, New Haven, CT, United States
  107. 107. Department of Medical Oncology, Yale School of Medicine, New Haven, CT, United States
  108. 108. University of Warwick, Warwick, United Kingdom
  109. 109. The Medical Oncology Centre of Rosebank, Johannesburg, South Africa
  110. 110. Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
  111. 111. Institute of Pathology, University Hospital Dusseldorf and Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany
  112. 112. Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
  113. 113. Departement de Medecine Oncologique, Institute Gustave Roussy, Villejuif, France
  114. 114. Department of Medicine, Yale University School of Medicine, New Haven, CT, United States
  115. 115. Department of Diagnostic and Theranostic Medicine, Institut Curie, University Paris-Sciences et Lettres, Paris, France
  116. 116. Integrated Pathology Unit, Institute of Cancer Research, London, United Kingdom
  117. 117. Precision Medicine Centre, Queen's University Belfast, Belfast, United Kingdom
  118. 118. Department of Biomedical Informatics, Stony Brook Medicine, New York, NY, United States
  119. 119. Department of Pathology, Aga Khan University, Nairobi, Kenya
  120. 120. Department of Pathology, Section of Breast Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  121. 121. Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Hopital Universitaire de Bruxelles (HUB), Universite Libre de Bruxelles (ULB), Brussels, Belgium
  122. 122. Medical Oncology Department, Institut Jules Bordet, Hopital Universitaire de Bruxelles (HUB), Universite Libre de Bruxelles, Brussels, Belgium
  123. 123. Institute of Pathology, University Hospital Heidelberg, Centers for Personalized Medicine (ZPM), Heidelberg, Germany
  124. 124. King Hussein Cancer Center, Amman, Jordan
  125. 125. Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu�, Cluj-Napoca, Romania
  126. 126. University of Texas MD Anderson Cancer Center, Houston, TX, United States
  127. 127. Kyoto University, Kyoto, Japan
  128. 128. Tempus Labs, Chicago, IL, United States
  129. 129. AI for Oncology Lab, Netherlands Cancer Institute, Amsterdam, Netherlands
  130. 130. Mayo Clinic, Jacksonville, FL, United States
  131. 131. Pathology, and Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
  132. 132. Department of Radiation Oncology, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  133. 133. Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands
  134. 134. Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
  135. 135. Johns Hopkins Oncology Center, Baltimore, MD, United States
  136. 136. Department of Pathology, European Institute of Oncology & University of Milan, Milan, Italy
  137. 137. Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, Coventry, United Kingdom
  138. 138. CellCarta NV, Antwerp, Belgium
  139. 139. Fudan Medical University Shanghai Cancer Center, Shanghai, China
  140. 140. Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
  141. 141. Department of Medicine, NYU Grossman School of Medicine, Manhattan, NY, United States
  142. 142. University of Edinburgh, Edinburgh, United Kingdom
  143. 143. Department of Medicine and Research, German Breast Group, Neu-Isenburg, Germany
  144. 144. Institut fur Pathologie, Philipps-Universitat Marburg und Universitatsklinikum Marburg, Marburg, Germany
  145. 145. Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Melbourne, VIC, Australia
  146. 146. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  147. 147. Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark
  148. 148. Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark

Source: Journal of Pathology Published:2023


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