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, David B; Broeckx, Glenn; Jahangir, Chowdhury Arif; Verbandt, Sara; Gupta, Rajarsi R; Thagaard, Jeppe; Khiroya, Reena; Kos, Zuzana; Abduljabbar, Khalid; Acosta Haab, Gabriela; Acs, Balazs; Almeida, Jonas S; Alvarado-Cabrero, Isabel; Azmoudeh-Ardalan, Farid; Badve, Sunil; Baharun, Nurkhairul Bariyah; Bellolio, Enrique R; Bheemaraju, Vydehi; Blenman, Kim Rm; Botinelly Mendonça Fujimoto, Luciana; Burgues, Octavio; Cheang, Maggie Chon U; Ciompi, Francesco; Cooper, Lee Ad; Coosemans, An; Corredor, Germán; Dantas Portela, Flavio Luis; Deman, Frederik; Demaria, Sandra; Dudgeon, Sarah N; Elghazawy, Mahmoud; Ely, Scott; Fernandez-Martín, Claudio; Fineberg, Susan; Fox, Stephen B; Gallagher, William M; Giltnane, Jennifer M; Gnjatic, Sacha; Gonzalez-Ericsson, Paula I; Grigoriadis, Anita; Halama, Niels; Hanna, Matthew G; Harbhajanka, Aparna; Hardas, Alexandros; Hart, Steven N; Hartman, Johan; Hewitt, Stephen; Hida, Akira I; Horlings, Hugo M; Husain, Zaheed; Hytopoulos, Evangelos; Irshad, Sheeba; Janssen, Emiel Am; Kahila, Mohamed; Kataoka, Tatsuki R; Kawaguchi, Kosuke; Kharidehal, Durga; Khramtsov, Andrey I; Kiraz, Umay; Kirtani, Pawan; Kodach, Liudmila L; Korski, Konstanty; Kovács, Anikó; Laenkholm, Anne-Vibeke; Lang-Schwarz, Corinna; Larsimont, Denis; Lennerz, Jochen K; Lerousseau, Marvin; Li, Xiaoxian; Ly, Amy; Madabhushi, Anant; Maley, Sai K; Manur Narasimhamurthy, Vidya; Marks, Douglas K; McDonald, Elizabeth S; Mehrotra, Ravi; Michiels, Stefan; Minhas, Fayyaz Ul Amir Afsar; Mittal, Shachi; Moore, David A; Mushtaq, Shamim; Nighat, Hussain; Papathomas, Thomas; Penault-Llorca, Frederique; Perera, Rashindrie D; Pinard, Christopher J; Pinto-Cardenas, Juan Carlos; Pruneri, Giancarlo; Pusztai, Lajos; Rahman, Arman; Rajpoot, Nasir Mahmood; Rapoport, Bernardo Leon; Rau, Tilman T; Reis-Filho, Jorge S; Ribeiro, Joana M; Rimm, David; Salomon, Anne-Vincent; Salto-Tellez, Manuel; Saltz, Joel; Sayed, Shahin; Siziopikou, Kalliopi P; Sotiriou, Christos; Stenzinger, Albrecht; Sughayer, Maher A; Sur, Daniel; Symmans, Fraser; Tanaka, Sunao; Taxter, Timothy; Tejpar, Sabine; Teuwen, Jonas; Thompson, E Aubrey; Tramm, Trine; Tran, William T; van der Laak, Jeroen; van Diest, Paul J; Verghese, Gregory E; Viale, Giuseppe; Vieth, Michael; Wahab, Noorul; Walter, Thomas; Waumans, Yannick; Wen, Hannah Y; Yang, Wentao; Yuan, Yinyin; Adams, Sylvia; Bartlett, John Mark Seaverns; Loibl, Sibylle; Denkert, Carsten; Savas, Peter; Loi, Sherene; Salgado, Roberto; Specht Stovgaard, Elisabeth; Akturk, Guray; Bouchmaa, Najat
(2023) Journal of Pathology, volume 260, issue 5, pp. 514 - 532
(Article)
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
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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.
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Keywords: Immunoscore, multispectral immunofluorescence, spatial heterogeneity, spatial statistics, sTIL score, TIL, tumor infiltrating lymphocytes, Pathology and Forensic Medicine, Review, Journal Article
ISSN: 0022-3417
Publisher: John Wiley and Sons Ltd
Note: Funding Information: This work was made possible through the donations of Walter Bowen (Portland, OR, USA) and others. The authors thank Torsten Nielsen, MD/PhD (Professor of Pathology & Laboratory Medicine, University of British Columbia) for critical revision of the manuscript. Acknowledgements of funds supporting co‐authors are as follows: GB: funded by the Gilead Breast Cancer Research Grant 2023. SV: supported by ‘Interne Fondsen KU Leuven/Internal Funds KU Leuven. BA: the Swedish Society for Medical Research (Svenska Sällskapet för Medicinsk Forskning) postdoctoral grant, Swedish Breast Cancer Association (Bröstcancerförbundet) research grant 2021. GC: the Peer Reviewed Cancer Research Program (award W81XWH‐21‐1‐0160) from the US Department of Defense and the Mayo Clinic Breast Cancer SPORE grant P50 CA116201 from the National Institutes of Health (NIH). CF‐M: Horizon 2020 European Union Research and Innovation Programme under the Marie Sklodowska Curie Grant agreement no. 860627 (CLARIFY Project). SBF: NHMRC GNT1193630. WMG: Higher Education Authority, Department of Further and Higher Education, Research, Innovation and Science and the Shared Island Fund (AICRIstart: A Foundation Stone for the All‐Island Cancer Research Institute [AICRI]: Building Critical Mass in Precision Cancer Medicine; https://www.aicri.org/aicristart ): Irish Cancer Society (Collaborative Cancer Research Centre BREAST‐PREDICT; CCRC13GAL; https://www.breastpredict.com ), the Science Foundation Ireland Investigator Programme (OPTi‐PREDICT; 15/IA/3104), the Science Foundation Ireland Strategic Partnership Programme (Precision Oncology Ireland; 18/SPP/3522; https://www.precisiononcology.ie ). SG: partially supported by National Institutes of Health (NIH) grant CA224319, DK124165, CA263705, and CA196521. AG: Breast Cancer Now (and their legacy charity Breakthrough Breast Cancer) and Cancer Research UK (CRUK/07/012, KCL‐BCN‐Q3). TRK: Japan Society for the Promotion of Science (JSPS) KAKENHI (21K06909). UK: Horizon 2020 European Union Research and Innovation Programme under the Marie Sklodowska Curie grant agreement no. 860627 (CLARIFY Project). JKL: part supported by NIH (R37 CA225655). AM: National Cancer Institute award numbers R01CA268287A1, U01CA269181, R01CA26820701A1, R01CA249992‐01A1, R01CA202752‐01A1, R01CA208236‐01A1, R01CA216579‐01A1, R01CA220581‐01A1, R01CA257612‐01A1, 1U01CA239055‐01, 1U01CA248226‐01, 1U54CA254566‐01, National Heart, Lung and Blood Institute 1R01HL15127701A1, R01HL15807101A1, National Institute of Biomedical Imaging and Bioengineering 1R43EB028736‐01, VA Merit Review Award IBX004121A from the US Department of Veterans Affairs Biomedical Laboratory Research and Development Service the Office of the Assistant Secretary of Defense for Health Affairs, through the Department of Defense Breast Cancer Research Program (W81XWH‐19‐1‐0668), the Prostate Cancer Research Program (W81XWH‐20‐1‐0851), the Lung Cancer Research Program (W81XWH‐18‐1‐0440, W81XWH‐20‐1‐0595), the Peer Reviewed Cancer Research Program (W81XWH‐18‐1‐0404, W81XWH‐21‐1‐0345, W81XWH‐21‐1‐0160), the Kidney Precision Medicine Project (KPMP) Glue Grant and sponsored research agreements from Bristol Myers‐Squibb, Boehringer‐Ingelheim, Eli‐Lilly, and AstraZeneca. SKM: Kay Pogue‐Geile, Director of Molecular Profiling at NSABP for her constant support and encouragement, Roberto Salgado, for getting me initiated into the wonderful subject of immuno‐oncology and its possibilities. FuAAM: EPSRC EP/W02909X/1 and PathLAKE consortium. FP‐L: Fondation ARC, La Ligue Contre le Cancer. RDP: the Melbourne Research Scholarship and a scholarship from the Peter MacCallum Cancer Centre. JSR‐F: part by the Breast Cancer Research Foundation, a Susan G Komen Leadership Grant, and the NIH/NCI P50 CA247749 01 grant. JS: National Cancer Institute grant UH3CA225021, U24CA215109. ST: ‘Interne Fondsen KU Leuven/Internal Funds KU Leuven. JT: institutional grants of the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. EAT: Breast Cancer Research Foundation grant 22‐161. GEV: Breast Cancer Now (and their legacy charity Breakthrough Breast Cancer) and Cancer Research UK (CRUK/07/012, KCL‐BCN‐Q3). TW: S French Government Under Management of Agence Nationale de la Recherche as part of the ‘Investissements d'avenir’ program, reference ANR‐19‐P3IA‐0001 (PRAIRIE 3IA Institute) and Q‐Life (ANR‐17‐CONV‐0005). HYW: in part by the NIH/NCI P50 CA247749 01 grant. YY: Cancer Research UK Career Establishment Award (CRUK C45982/A21808). PS: National Health and Medical Research Council, Australia. SL: National Breast Cancer Foundation of Australia (NBCF) (APP ID: EC‐17‐001), the Breast Cancer Research Foundation, New York (BCRF [APP ID: BCRF‐21‐102]), and a National Health and Medical Council of Australia (NHMRC) Investigator Grant (APP ID: 1162318). RS: Breast Cancer Research Foundation (BCRF, grant no. 17‐194). Funding Information: This work was made possible through the donations of Walter Bowen (Portland, OR, USA) and others. The authors thank Torsten Nielsen, MD/PhD (Professor of Pathology & Laboratory Medicine, University of British Columbia) for critical revision of the manuscript. Acknowledgements of funds supporting co-authors are as follows: GB: funded by the Gilead Breast Cancer Research Grant 2023. SV: supported by ‘Interne Fondsen KU Leuven/Internal Funds KU Leuven. BA: the Swedish Society for Medical Research (Svenska Sällskapet för Medicinsk Forskning) postdoctoral grant, Swedish Breast Cancer Association (Bröstcancerförbundet) research grant 2021. GC: the Peer Reviewed Cancer Research Program (award W81XWH-21-1-0160) from the US Department of Defense and the Mayo Clinic Breast Cancer SPORE grant P50 CA116201 from the National Institutes of Health (NIH). CF-M: Horizon 2020 European Union Research and Innovation Programme under the Marie Sklodowska Curie Grant agreement no. 860627 (CLARIFY Project). SBF: NHMRC GNT1193630. WMG: Higher Education Authority, Department of Further and Higher Education, Research, Innovation and Science and the Shared Island Fund (AICRIstart: A Foundation Stone for the All-Island Cancer Research Institute [AICRI]: Building Critical Mass in Precision Cancer Medicine; https://www.aicri.org/aicristart): Irish Cancer Society (Collaborative Cancer Research Centre BREAST-PREDICT; CCRC13GAL; https://www.breastpredict.com), the Science Foundation Ireland Investigator Programme (OPTi-PREDICT; 15/IA/3104), the Science Foundation Ireland Strategic Partnership Programme (Precision Oncology Ireland; 18/SPP/3522; https://www.precisiononcology.ie). SG: partially supported by National Institutes of Health (NIH) grant CA224319, DK124165, CA263705, and CA196521. Publisher Copyright: © 2023 The Pathological Society of Great Britain and Ireland.
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