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

doi:10.1002/path.6165

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. BlenmanLuciana 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

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Review article › peer-review

7 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 language	English (US)
Pages (from-to)	514-532
Number of pages	19
Journal	Journal of Pathology
Volume	260
Issue number	5
DOIs	https://doi.org/10.1002/path.6165
State	Published - Aug 2023

Funding

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). 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.

Keywords

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

ASJC Scopus subject areas

Pathology and Forensic Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/path.6165

Cite this

Page, D. B., Broeckx, G., Jahangir, C. A., Verbandt, S., Gupta, R. R., Thagaard, J., Khiroya, R., Kos, Z., Abduljabbar, K., Acosta Haab, G., Acs, B., Akturk, G., Almeida, J. S., Alvarado-Cabrero, I., Azmoudeh-Ardalan, F., Badve, S., Baharun, N. B., Bellolio, E. R., Bheemaraju, V., ... Specht Stovgaard, E. (2023). 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. Journal of Pathology, 260(5), 514-532. https://doi.org/10.1002/path.6165

@article{74967c89958e47bfac2398b272f3c548,

title = "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",

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.",

keywords = "Immunoscore, TIL, multispectral immunofluorescence, sTIL score, spatial heterogeneity, spatial statistics, tumor infiltrating lymphocytes",

author = "Page, {David B.} and Glenn Broeckx and Jahangir, {Chowdhury Arif} and Sara Verbandt and Gupta, {Rajarsi R.} and Jeppe Thagaard and Reena Khiroya and Zuzana Kos and Khalid Abduljabbar and {Acosta Haab}, Gabriela and Balazs Acs and Guray Akturk and Almeida, {Jonas S.} and Isabel Alvarado-Cabrero and Farid Azmoudeh-Ardalan and Sunil Badve and Baharun, {Nurkhairul Bariyah} and Bellolio, {Enrique R.} and Vydehi Bheemaraju and Blenman, {Kim R.M.} and {Botinelly Mendon{\c c}a Fujimoto}, Luciana and Najat Bouchmaa and Octavio Burgues and Cheang, {Maggie Chon U.} and Francesco Ciompi and Cooper, {Lee A.D.} and An Coosemans and Germ{\'a}n Corredor and {Dantas Portela}, {Flavio Luis} and Frederik Deman and Sandra Demaria and Dudgeon, {Sarah N.} and Mahmoud Elghazawy and Scott Ely and Claudio Fernandez-Mart{\'i}n and Susan Fineberg and Fox, {Stephen B.} and Gallagher, {William M.} and Giltnane, {Jennifer M.} and Sacha Gnjatic and Gonzalez-Ericsson, {Paula I.} and Anita Grigoriadis and Niels Halama and Hanna, {Matthew G.} and Aparna Harbhajanka and Alexandros Hardas and Hart, {Steven N.} and Johan Hartman and Stephen Hewitt and Hida, {Akira I.} and Horlings, {Hugo M.} and Zaheed Husain and Evangelos Hytopoulos and Sheeba Irshad and Janssen, {Emiel A.M.} and Mohamed Kahila and Kataoka, {Tatsuki R.} and Kosuke Kawaguchi and Durga Kharidehal and Khramtsov, {Andrey I.} and Umay Kiraz and Pawan Kirtani and Kodach, {Liudmila L.} and Konstanty Korski and Anik{\'o} Kov{\'a}cs and Laenkholm, {Anne Vibeke} and Corinna Lang-Schwarz and Denis Larsimont and Lennerz, {Jochen K.} and Marvin Lerousseau and Xiaoxian Li and Amy Ly and Anant Madabhushi and Maley, {Sai K.} and {Manur Narasimhamurthy}, Vidya and Marks, {Douglas K.} and McDonald, {Elizabeth S.} and Ravi Mehrotra and Stefan Michiels and Minhas, {Fayyaz ul Amir Afsar} and Shachi Mittal and Moore, {David A.} and Shamim Mushtaq and Hussain Nighat and Thomas Papathomas and Frederique Penault-Llorca and Perera, {Rashindrie D.} and Pinard, {Christopher J.} and Pinto-Cardenas, {Juan Carlos} and Giancarlo Pruneri and Lajos Pusztai and Arman Rahman and Rajpoot, {Nasir Mahmood} and Rapoport, {Bernardo Leon} and Rau, {Tilman T.} and Reis-Filho, {Jorge S.} and Ribeiro, {Joana M.} and David Rimm and Anne Vincent-Salomon and Manuel Salto-Tellez and Joel Saltz and Shahin Sayed and Siziopikou, {Kalliopi P.} and Christos Sotiriou and Albrecht Stenzinger and Sughayer, {Maher A.} and Daniel Sur and Fraser Symmans and Sunao Tanaka and Timothy Taxter and Sabine Tejpar and Jonas Teuwen and Thompson, {E. Aubrey} and Trine Tramm and Tran, {William T.} and {van der Laak}, Jeroen and {van Diest}, {Paul J.} and Verghese, {Gregory E.} and Giuseppe Viale and Michael Vieth and Noorul Wahab and Thomas Walter and Yannick Waumans and Wen, {Hannah Y.} and Wentao Yang and Yinyin Yuan and Sylvia Adams and Bartlett, {John Mark Seaverns} and Sibylle Loibl and Carsten Denkert and Peter Savas and Sherene Loi and Roberto Salgado and {Specht Stovgaard}, Elisabeth",

note = "Publisher Copyright: {\textcopyright} 2023 The Pathological Society of Great Britain and Ireland.",

year = "2023",

month = aug,

doi = "10.1002/path.6165",

language = "English (US)",

volume = "260",

pages = "514--532",

journal = "Journal of Pathology",

issn = "0022-3417",

publisher = "John Wiley and Sons Ltd",

number = "5",

}

Page, DB, Broeckx, G, Jahangir, CA, Verbandt, S, Gupta, RR, Thagaard, J, Khiroya, R, Kos, Z, Abduljabbar, K, Acosta Haab, G, Acs, B, Akturk, G, Almeida, JS, Alvarado-Cabrero, I, Azmoudeh-Ardalan, F, Badve, S, Baharun, NB, Bellolio, ER, Bheemaraju, V, Blenman, KRM, Botinelly Mendonça Fujimoto, L, Bouchmaa, N, Burgues, O, Cheang, MCU, Ciompi, F, Cooper, LAD, Coosemans, A, Corredor, G, Dantas Portela, FL, Deman, F, Demaria, S, Dudgeon, SN, Elghazawy, M, Ely, S, Fernandez-Martín, C, Fineberg, S, Fox, SB, Gallagher, WM, Giltnane, JM, Gnjatic, S, Gonzalez-Ericsson, PI, Grigoriadis, A, Halama, N, Hanna, MG, Harbhajanka, A, Hardas, A, Hart, SN, Hartman, J, Hewitt, S, Hida, AI, Horlings, HM, Husain, Z, Hytopoulos, E, Irshad, S, Janssen, EAM, Kahila, M, Kataoka, TR, Kawaguchi, K, Kharidehal, D, Khramtsov, AI, Kiraz, U, Kirtani, P, Kodach, LL, Korski, K, Kovács, A, Laenkholm, AV, Lang-Schwarz, C, Larsimont, D, Lennerz, JK, Lerousseau, M, Li, X, Ly, A, Madabhushi, A, Maley, SK, Manur Narasimhamurthy, V, Marks, DK, McDonald, ES, Mehrotra, R, Michiels, S, Minhas, FUAA, Mittal, S, Moore, DA, Mushtaq, S, Nighat, H, Papathomas, T, Penault-Llorca, F, Perera, RD, Pinard, CJ, Pinto-Cardenas, JC, Pruneri, G, Pusztai, L, Rahman, A, Rajpoot, NM, Rapoport, BL, Rau, TT, Reis-Filho, JS, Ribeiro, JM, Rimm, D, Vincent-Salomon, A, Salto-Tellez, M, Saltz, J, Sayed, S, Siziopikou, KP, Sotiriou, C, Stenzinger, A, Sughayer, MA, Sur, D, Symmans, F, Tanaka, S, Taxter, T, Tejpar, S, Teuwen, J, Thompson, EA, Tramm, T, Tran, WT, van der Laak, J, van Diest, PJ, Verghese, GE, Viale, G, Vieth, M, Wahab, N, Walter, T, Waumans, Y, Wen, HY, Yang, W, Yuan, Y, Adams, S, Bartlett, JMS, Loibl, S, Denkert, C, Savas, P, Loi, S, Salgado, R & Specht Stovgaard, E 2023, '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', Journal of Pathology, vol. 260, no. 5, pp. 514-532. https://doi.org/10.1002/path.6165

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 et al.
In: Journal of Pathology, Vol. 260, No. 5, 08.2023, p. 514-532.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Spatial analyses of immune cell infiltration in cancer

T2 - current methods and future directions. A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

AU - Page, David B.

AU - Broeckx, Glenn

AU - Jahangir, Chowdhury Arif

AU - Verbandt, Sara

AU - Gupta, Rajarsi R.

AU - Thagaard, Jeppe

AU - Khiroya, Reena

AU - Kos, Zuzana

AU - Abduljabbar, Khalid

AU - Acosta Haab, Gabriela

AU - Acs, Balazs

AU - Akturk, Guray

AU - Almeida, Jonas S.

AU - Alvarado-Cabrero, Isabel

AU - Azmoudeh-Ardalan, Farid

AU - Badve, Sunil

AU - Baharun, Nurkhairul Bariyah

AU - Bellolio, Enrique R.

AU - Bheemaraju, Vydehi

AU - Blenman, Kim R.M.

AU - Botinelly Mendonça Fujimoto, Luciana

AU - Bouchmaa, Najat

AU - Burgues, Octavio

AU - Cheang, Maggie Chon U.

AU - Ciompi, Francesco

AU - Cooper, Lee A.D.

AU - Coosemans, An

AU - Corredor, Germán

AU - Dantas Portela, Flavio Luis

AU - Deman, Frederik

AU - Demaria, Sandra

AU - Dudgeon, Sarah N.

AU - Elghazawy, Mahmoud

AU - Ely, Scott

AU - Fernandez-Martín, Claudio

AU - Fineberg, Susan

AU - Fox, Stephen B.

AU - Gallagher, William M.

AU - Giltnane, Jennifer M.

AU - Gnjatic, Sacha

AU - Gonzalez-Ericsson, Paula I.

AU - Grigoriadis, Anita

AU - Halama, Niels

AU - Hanna, Matthew G.

AU - Harbhajanka, Aparna

AU - Hardas, Alexandros

AU - Hart, Steven N.

AU - Hartman, Johan

AU - Hewitt, Stephen

AU - Hida, Akira I.

AU - Horlings, Hugo M.

AU - Husain, Zaheed

AU - Hytopoulos, Evangelos

AU - Irshad, Sheeba

AU - Janssen, Emiel A.M.

AU - Kahila, Mohamed

AU - Kataoka, Tatsuki R.

AU - Kawaguchi, Kosuke

AU - Kharidehal, Durga

AU - Khramtsov, Andrey I.

AU - Kiraz, Umay

AU - Kirtani, Pawan

AU - Kodach, Liudmila L.

AU - Korski, Konstanty

AU - Kovács, Anikó

AU - Laenkholm, Anne Vibeke

AU - Lang-Schwarz, Corinna

AU - Larsimont, Denis

AU - Lennerz, Jochen K.

AU - Lerousseau, Marvin

AU - Li, Xiaoxian

AU - Ly, Amy

AU - Madabhushi, Anant

AU - Maley, Sai K.

AU - Manur Narasimhamurthy, Vidya

AU - Marks, Douglas K.

AU - McDonald, Elizabeth S.

AU - Mehrotra, Ravi

AU - Michiels, Stefan

AU - Minhas, Fayyaz ul Amir Afsar

AU - Mittal, Shachi

AU - Moore, David A.

AU - Mushtaq, Shamim

AU - Nighat, Hussain

AU - Papathomas, Thomas

AU - Penault-Llorca, Frederique

AU - Perera, Rashindrie D.

AU - Pinard, Christopher J.

AU - Pinto-Cardenas, Juan Carlos

AU - Pruneri, Giancarlo

AU - Pusztai, Lajos

AU - Rahman, Arman

AU - Rajpoot, Nasir Mahmood

AU - Rapoport, Bernardo Leon

AU - Rau, Tilman T.

AU - Reis-Filho, Jorge S.

AU - Ribeiro, Joana M.

AU - Rimm, David

AU - Vincent-Salomon, Anne

AU - Salto-Tellez, Manuel

AU - Saltz, Joel

AU - Sayed, Shahin

AU - Siziopikou, Kalliopi P.

AU - Sotiriou, Christos

AU - Stenzinger, Albrecht

AU - Sughayer, Maher A.

AU - Sur, Daniel

AU - Symmans, Fraser

AU - Tanaka, Sunao

AU - Taxter, Timothy

AU - Tejpar, Sabine

AU - Teuwen, Jonas

AU - Thompson, E. Aubrey

AU - Tramm, Trine

AU - Tran, William T.

AU - van der Laak, Jeroen

AU - van Diest, Paul J.

AU - Verghese, Gregory E.

AU - Viale, Giuseppe

AU - Vieth, Michael

AU - Wahab, Noorul

AU - Walter, Thomas

AU - Waumans, Yannick

AU - Wen, Hannah Y.

AU - Yang, Wentao

AU - Yuan, Yinyin

AU - Adams, Sylvia

AU - Bartlett, John Mark Seaverns

AU - Loibl, Sibylle

AU - Denkert, Carsten

AU - Savas, Peter

AU - Loi, Sherene

AU - Salgado, Roberto

AU - Specht Stovgaard, Elisabeth

PY - 2023/8

Y1 - 2023/8

N2 - 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.

AB - 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.

KW - Immunoscore

KW - TIL

KW - multispectral immunofluorescence

KW - sTIL score

KW - spatial heterogeneity

KW - spatial statistics

KW - tumor infiltrating lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=85167992595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85167992595&partnerID=8YFLogxK

U2 - 10.1002/path.6165

DO - 10.1002/path.6165

M3 - Review article

C2 - 37608771

AN - SCOPUS:85167992595

SN - 0022-3417

VL - 260

SP - 514

EP - 532

JO - Journal of Pathology

JF - Journal of Pathology

IS - 5

ER -

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

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