Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer

Author:

Jahangir Chowdhury Arif1ORCID,Page David B2ORCID,Broeckx Glenn34,Gonzalez Claudia A1,Burke Caoimbhe1,Murphy Clodagh1,Reis‐Filho Jorge S5ORCID,Ly Amy6,Harms Paul W7,Gupta Rajarsi R8ORCID,Vieth Michael9,Hida Akira I10,Kahila Mohamed11,Kos Zuzana12,van Diest Paul J1314,Verbandt Sara15,Thagaard Jeppe1617,Khiroya Reena18,Abduljabbar Khalid19,Acosta Haab Gabriela20,Acs Balazs2122,Adams Sylvia2324,Almeida Jonas S25,Alvarado‐Cabrero Isabel26,Azmoudeh‐Ardalan Farid27,Badve Sunil28,Baharun Nurkhairul Bariyah29,Bellolio Enrique R30,Bheemaraju Vydehi31,Blenman Kim RM3233,Botinelly Mendonça Fujimoto Luciana34,Burgues Octavio35,Chardas Alexandros36ORCID,Cheang Maggie Chon U37,Ciompi Francesco38,Cooper Lee AD39,Coosemans An40,Corredor Germán41,Dantas Portela Flavio Luis42ORCID,Deman Frederik3,Demaria Sandra4344,Dudgeon Sarah N45,Elghazawy Mahmoud4647ORCID,Fernandez‐Martín Claudio48,Fineberg Susan49,Fox Stephen B50,Giltnane Jennifer M51,Gnjatic Sacha52,Gonzalez‐Ericsson Paula I53ORCID,Grigoriadis Anita5455ORCID,Halama Niels56,Hanna Matthew G57,Harbhajanka Aparna58,Hart Steven N59ORCID,Hartman Johan2260ORCID,Hewitt Stephen61,Horlings Hugo M62,Husain Zaheed63,Irshad Sheeba64,Janssen Emiel AM6566,Kataoka Tatsuki R67ORCID,Kawaguchi Kosuke68,Khramtsov Andrey I69,Kiraz Umay6566,Kirtani Pawan70,Kodach Liudmila L71,Korski Konstanty72,Akturk Guray73,Scott Ely74,Kovács Anikó7576,Lænkholm Anne‐Vibeke7778,Lang‐Schwarz Corinna9,Larsimont Denis79,Lennerz Jochen K80,Lerousseau Marvin818283,Li Xiaoxian84,Madabhushi Anant85,Maley Sai K86,Manur Narasimhamurthy Vidya87,Marks Douglas K23,McDonald Elizabeth S88,Mehrotra Ravi8990,Michiels Stefan91,Kharidehal Durga92,Minhas Fayyaz ul Amir Afsar93,Mittal Shachi94,Moore David A95,Mushtaq Shamim96,Nighat Hussain97,Papathomas Thomas9899,Penault‐Llorca Frederique100,Perera Rashindrie D101102,Pinard Christopher J103104105106,Pinto‐Cardenas Juan Carlos107,Pruneri Giancarlo108109,Pusztai Lajos110111,Rajpoot Nasir Mahmood112,Rapoport Bernardo Leon113114,Rau Tilman T115ORCID,Ribeiro Joana M116,Rimm David117118ORCID,Vincent‐Salomon Anne119,Saltz Joel120,Sayed Shahin121,Hytopoulos Evangelos121122,Mahon Sarah123,Siziopikou Kalliopi P124,Sotiriou Christos125126,Stenzinger Albrecht127,Sughayer Maher A128,Sur Daniel129,Symmans Fraser130,Tanaka Sunao131,Taxter Timothy132,Tejpar Sabine15,Teuwen Jonas133,Thompson E Aubrey134,Tramm Trine135,Tran William T136,van der Laak Jeroen37,Verghese Gregory E5455ORCID,Viale Giuseppe137,Wahab Noorul138ORCID,Walter Thomas818283,Waumans Yannick139,Wen Hannah Y57,Yang Wentao140,Yuan Yinyin141,Bartlett John142,Loibl Sibylle143,Denkert Carsten144,Savas Peter145146,Loi Sherene145147,Specht Stovgaard Elisabeth148,Salgado Roberto3145,Gallagher William M1,Rahman Arman149

Affiliation:

1. UCD School of Biomolecular and Biomedical Science UCD Conway Institute, University College Dublin Dublin Ireland

2. Earle A Chiles Research Institute, Providence Cancer Institute Portland OR USA

3. Department of Pathology PA2 GZA‐ZNA Hospitals Antwerp Belgium

4. Centre for Oncological Research (CORE), MIPPRO, Faculty of Medicine Antwerp University Antwerp Belgium

5. Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA

6. Department of Pathology Massachusetts General Hospital Boston MA USA

7. Departments of Pathology and Dermatology University of Michigan Ann Arbor MI USA

8. Department of Biomedical Informatics Stony Brook University Stony Brook NY USA

9. Institute of Pathology, Klinikum Bayreuth GmbH Friedrich‐Alexander‐University Erlangen‐Nuremberg Bayreuth Germany

10. Department of Pathology Matsuyama Shimin Hospital Matsuyama Japan

11. Department of Pathology Yale School of Medicine New Haven CT USA

12. Department of Pathology and Laboratory Medicine University of British Columbia, BC Cancer Vancouver British Columbia Canada

13. Department of Pathology University Medical Center Utrecht Utrecht The Netherlands

14. Johns Hopkins Oncology Center Baltimore MD USA

15. Digestive Oncology, Department of Oncology KU Leuven Leuven Belgium

16. Technical University of Denmark Kgs. Lyngby Denmark

17. Visiopharm A/S Hørsholm Denmark

18. Department of Cellular Pathology University College Hospital London UK

19. Centre for Evolution and Cancer The Institute of Cancer Research London UK

20. Hospital Maria Curie Buenos Aires Argentina

21. Department of Oncology and Pathology Karolinska Institutet Stockholm Sweden

22. Department of Clinical Pathology and Cancer Diagnostics Karolinska University Hospital Stockholm Sweden

23. Perlmutter Cancer Center, NYU Langone Health New York NY USA

24. Department of Medicine NYU Grossman School of Medicine Manhattan NY USA

25. Division of Cancer Epidemiology and Genetics (DCEG) National Cancer Institute (NCI) Rockville MD USA

26. Oncology Hospital, Star Medica Centro Juarez City Mexico

27. Tehran University of Medical Sciences Tehran Iran

28. Department of Pathology and Laboratory Medicine Emory University School of Medicine, Emory University Winship Cancer Institute Atlanta GA USA

29. The National University of Malaysia Kuala Lumpur Malaysia

30. Departamento de Anatomía Patológica, Facultad de Medicina Universidad de La Frontera Temuco Chile

31. Department of Pathology Narayana Medical College Nellore India

32. Department of Internal Medicine Section of Medical Oncology and Yale Cancer Center Yale School of Medicine New Haven CT USA

33. Department of Computer Science Yale School of Engineering and Applied Science New Haven CT USA

34. Amazonas Federal University Manaus Brazil

35. Pathology Department Hospital Cliníco Universitario de Valencia/Incliva Valencia Spain

36. Department of Pathobiology & Population Sciences The Royal Veterinary College London UK

37. Head of Integrative Genomics Analysis in Clinical Trials, ICR‐CTSU, Division of Clinical Studies The Institute of Cancer Research London UK

38. Department of Pathology Radboud University Medical Center Nijmegen The Netherlands

39. Department of Pathology Northwestern Feinberg School of Medicine Chicago IL USA

40. Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy KU Leuven Leuven Belgium

41. Biomedical Engineering Department Emory University Atlanta GA USA

42. Hospital Universitário Getúlio Vargas Manaus Brazil

43. Department of Radiation Oncology Weill Cornell Medical College New York NY USA

44. Department of Pathology Weill Cornell Medicine New York NY USA

45. Computational Biology and Bioinformatics Yale University New Haven CT USA

46. University of Surrey Guildford UK

47. Ain Shams University Cairo Egypt

48. Instituto Universitario de Investigación en Tecnología Centrada en el Ser Humano, HUMAN‐tech, Universitat Politècnica de València Valencia Spain

49. Montefiore Medical Center and the Albert Einstein College of Medicine New York NY USA

50. Pathology, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology University of Melbourne Melbourne Victoria Australia

51. Genentech San Francisco CA USA

52. 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

53. Department of Medicine Vanderbilt University Medical Center Nashville TN USA

54. Cancer Bioinformatics, Faculty of Life Sciences and Medicine School of Cancer & Pharmaceutical Sciences, King's College London London UK

55. The Breast Cancer Now Research Unit, Faculty of Life Sciences and Medicine School of Cancer and Pharmaceutical Sciences, King's College London London UK

56. Department of Translational Immunotherapy German Cancer Research Center Heidelberg Germany

57. Memorial Sloan Kettering Cancer Center New York NY USA

58. Case Western University Cleveland OH USA

59. Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA

60. Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden

61. Laboratory of Pathology, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda MD USA

62. Division of Pathology Netherlands Cancer Institute (NKI) Amsterdam The Netherlands

63. Praava Health Dhaka Bangladesh

64. King's College London & Guys & St Thomas NHS Trust London UK

65. Department of Pathology Stavanger University Hospital Stavanger Norway

66. Department of Chemistry, Bioscience and Environmental Technology University of Stavanger Stavanger Norway

67. Department of Pathology Iwate Medical University Morioka Japan

68. Department of Breast Surgery Kyoto University Graduate School of Medicine Kyoto Japan

69. Department of Pathology and Laboratory Medicine Ann & Robert H. Lurie Children's Hospital of Chicago Chicago IL USA

70. Histopathology Aakash Healthcare Super Speciality Hospital New Delhi India

71. Department of Pathology Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands

72. Data, Analytics and Imaging, Product Development, F. Hoffmann‐La Roche AG Basel Switzerland

73. Translational Molecular Biomarkers, Merck & Co., Inc. Kenilworth NJ USA

74. Translational Medicine, Bristol Myers Squibb Princeton NJ USA

75. Department of Clinical Pathology Sahlgrenska University Hospital Gothenburg Sweden

76. Institute of Biomedicine, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

77. Department of Surgical Pathology Zealand University Hospital Roskilde Denmark

78. Department of Surgical Pathology University of Copenhagen Copenhagen Denmark

79. Institut Jules Bordet Université Libre de Bruxelles Brussels Belgium

80. Center for Integrated Diagnostics, Massachusetts General Hospital/Harvard Medical School Boston MA USA

81. Centre for Computational Biology (CBIO), Mines Paris PSL University Paris France

82. Institut Curie PSL University Paris France

83. INSERM U900 Paris France

84. Department of Pathology and Laboratory Medicine Emory University Atlanta GA USA

85. Department of Biomedical Engineering, Radiology and Imaging Sciences, Biomedical Informatics, Pathology Georgia Institute of Technology and Emory University Atlanta GA USA

86. NRG Oncology/NSABP Foundation Pittsburgh PA USA

87. Manipal Hospitals Bangalore India

88. Breast Cancer Translational Research Group University of Pennsylvania Philadelphia PA USA

89. Indian Cancer Genomic Atlas Pune India

90. Centre for Health, Innovation and Policy Foundation Noida India

91. Office of Biostatistics and Epidemiology, Gustave Roussy, Oncostat U1018, Inserm University Paris‐Saclay, Ligue Contre le Cancer labeled Team Villejuif France

92. Department of Pathology Narayana Medical College and Hospital Nellore India

93. Tissue Image Analytics Centre, Warwick Cancer Research Centre, PathLAKE Consortium, Department of Computer Science University of Warwick Coventry UK

94. Department of Chemical Engineering, Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA

95. CRUK Lung Cancer Centre of Excellence, UCL and Cellular Pathology Department, UCLH London UK

96. Department of Biochemistry Ziauddin University Karachi Pakistan

97. Pathology and Laboratory Medicine All India Institute of Medical Sciences Raipur India

98. Institute of Metabolism and Systems Research University of Birmingham Birmingham UK

99. Department of Clinical Pathology Drammen Sykehus, Vestre Viken HF Drammen Norway

100. Service de Pathologie et Biopathologie Centre Jean PERRIN, INSERM U1240 Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne Clermont‐Ferrand France

101. School of Electrical, Mechanical and Infrastructure Engineering University of Melbourne Melbourne Victoria Australia

102. Division of Cancer Research, Peter MacCallum Cancer Centre Melbourne Victoria Australia

103. Radiogenomics Laboratory, Sunnybrook Health Sciences Centre Toronto Ontario Canada

104. Department of Clinical Studies, Ontario Veterinary College University of Guelph Guelph Ontario Canada

105. Department of Oncology Lakeshore Animal Health Partners Mississauga Ontario Canada

106. Centre for Advancing Responsible and Ethical Artificial Intelligence (CARE‐AI) University of Guelph Guelph Ontario Canada

107. Diagnostico de Salud Animal SA Ciudad de México Mexico

108. Department of Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

109. Faculty of Medicine and Surgery University of Milan Milan Italy

110. Yale Cancer Center Yale University New Haven CT USA

111. Department of Medical Oncology, Yale School of Medicine Yale University New Haven CT USA

112. University of Warwick Coventry UK

113. The Medical Oncology Centre of Rosebank Johannesburg South Africa

114. Department of Immunology, Faculty of Health Sciences University of Pretoria Pretoria South Africa

115. Institute of Pathology University Hospital Düsseldorf and Heinrich‐Heine‐University Düsseldorf Germany

116. Breast Unit Institute Gustave Roussy Villejuif France

117. Department of Pathology Yale University School of Medicine New Haven CT USA

118. Department of Medicine Yale University School of Medicine New Haven CT USA

119. Department of Diagnostic and Theranostic Medicine, Institut Curie University Paris‐Sciences et Lettres Paris France

120. Department of Biomedical Informatics, Stony Brook Medicine New York NY USA

121. Department of Pathology Aga Khan University Nairobi Kenya

122. iRhythm Technologies Inc. San Francisco CA USA

123. Mater Misericordiae University Hospital Dublin Ireland

124. Department of Pathology, Section of Breast Pathology Northwestern University Feinberg School of Medicine Chicago IL USA

125. Breast Cancer Translational Research Laboratory J.‐C. Heuson, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) Université Libre de Bruxelles (ULB) Brussels Belgium

126. Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) Université Libre de Bruxelles (ULB) Brussels Belgium

127. Institute of Pathology, University Hospital Heidelberg, Centers for Personalized Medicine (ZPM) Heidelberg Germany

128. King Hussein Cancer Center Amman Jordan

129. Department of Medical Oncology University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj‐Napoca Romania

130. University of Texas MD Anderson Cancer Center Houston TX USA

131. Kyoto University Kyoto Japan

132. Tempus Labs Chicago IL USA

133. AI for Oncology Lab The Netherlands Cancer Institute Amsterdam The Netherlands

134. Mayo Clinic Jacksonville FL USA

135. Department of Pathology Institute of Clinical Medicine, Aarhus University Hospital Aarhus Denmark

136. Department of Radiation Oncology University of Toronto and Sunnybrook Health Sciences Centre Toronto Canada

137. Department of Pathology European Institute of Oncology & University of Milan Milan Italy

138. Tissue Image Analytics Centre, Department of Computer Science University of Warwick Coventry UK

139. CellCarta NV Antwerp Belgium

140. Fudan Medical University Shanghai Cancer Center Shanghai PR China

141. Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine The University of Texas MD Anderson Cancer Center Houston TX USA

142. University of Edinburgh Edinburgh UK

143. Department of Medicine and Research German Breast Group Neu‐Isenburg Germany

144. Institut für Pathologie, Philipps‐Universität Marburg und Universitätsklinikum Marburg Marburg Germany

145. Division of Cancer Research Peter MacCallum Cancer Centre Melbourne Victoria Australia

146. The Sir Peter MacCallum Department of Medical Oncology University of Melbourne Melbourne Victoria Australia

147. Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne Victoria Australia

148. Department of Pathology, Herlev and Gentofte Hospital Herlev Denmark

149. UCD School of Medicine, UCD Conway Institute University College Dublin Dublin Ireland

Abstract

AbstractRecent advances in the field of immuno‐oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high‐throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi‐marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Funder

Breast Cancer Research Foundation

Svenska Sällskapet för Medicinsk Forskning

U.S. Department of Defense

National Health and Medical Research Council

National Institutes of Health

Cancer Research UK

Japan Society for the Promotion of Science

National Cancer Institute

National Institute of Biomedical Imaging and Bioengineering

California Breast Cancer Research Program

DOD Prostate Cancer Research Program

Engineering and Physical Sciences Research Council

Peter MacCallum Cancer Centre

KWF Kankerbestrijding

Ministerie van Volksgezondheid, Welzijn en Sport

Agence Nationale de la Recherche

Irish Cancer Society

Publisher

Wiley

Subject

Pathology and Forensic Medicine

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