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Establishing standardized immune phenotyping of metastatic melanoma by digital pathology

CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically “hot”), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune inf...

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Autores principales: Sobottka, Bettina, Nowak, Marta, Frei, Anja Laura, Haberecker, Martina, Merki, Samuel, Levesque, Mitchell P., Dummer, Reinhard, Moch, Holger, Koelzer, Viktor Hendrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590976/
https://www.ncbi.nlm.nih.gov/pubmed/34446805
http://dx.doi.org/10.1038/s41374-021-00653-y
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author Sobottka, Bettina
Nowak, Marta
Frei, Anja Laura
Haberecker, Martina
Merki, Samuel
Levesque, Mitchell P.
Dummer, Reinhard
Moch, Holger
Koelzer, Viktor Hendrik
author_facet Sobottka, Bettina
Nowak, Marta
Frei, Anja Laura
Haberecker, Martina
Merki, Samuel
Levesque, Mitchell P.
Dummer, Reinhard
Moch, Holger
Koelzer, Viktor Hendrik
author_sort Sobottka, Bettina
collection PubMed
description CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically “hot”), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune infiltrate called immune desert or excluded (clinically “cold”). Nevertheless, quantitative and reproducible methods examining their prevalence within tumors are lacking. We therefore established a computational diagnostic algorithm to quantitatively measure spatial densities of tumor-infiltrating CD8+ T cells by digital pathology within the three known tumor compartments as recommended by the International Immuno-Oncology Biomarker Working Group in 116 prospective metastatic melanomas of the Swiss Tumor Profiler cohort. Workflow robustness was confirmed in 33 samples of an independent retrospective validation cohort. The introduction of the intratumoral tumor center compartment proved to be most relevant for establishing an immune diagnosis in metastatic disease, independent of metastatic site. Cut-off values for reproducible classification were defined and successfully assigned densities into the respective immune diagnostic category in the validation cohort with high sensitivity, specificity, and precision. We provide a robust diagnostic algorithm based on intratumoral and stromal CD8+ T-cell densities in the tumor center compartment that translates spatial densities of tumor-infiltrating CD8+ T cells into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. The consideration of the intratumoral tumor center compartment allows immune phenotyping in the clinically highly relevant setting of metastatic lesions, even if the invasive margin compartment is not captured in biopsy material.
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spelling pubmed-85909762021-11-23 Establishing standardized immune phenotyping of metastatic melanoma by digital pathology Sobottka, Bettina Nowak, Marta Frei, Anja Laura Haberecker, Martina Merki, Samuel Levesque, Mitchell P. Dummer, Reinhard Moch, Holger Koelzer, Viktor Hendrik Lab Invest Article CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically “hot”), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune infiltrate called immune desert or excluded (clinically “cold”). Nevertheless, quantitative and reproducible methods examining their prevalence within tumors are lacking. We therefore established a computational diagnostic algorithm to quantitatively measure spatial densities of tumor-infiltrating CD8+ T cells by digital pathology within the three known tumor compartments as recommended by the International Immuno-Oncology Biomarker Working Group in 116 prospective metastatic melanomas of the Swiss Tumor Profiler cohort. Workflow robustness was confirmed in 33 samples of an independent retrospective validation cohort. The introduction of the intratumoral tumor center compartment proved to be most relevant for establishing an immune diagnosis in metastatic disease, independent of metastatic site. Cut-off values for reproducible classification were defined and successfully assigned densities into the respective immune diagnostic category in the validation cohort with high sensitivity, specificity, and precision. We provide a robust diagnostic algorithm based on intratumoral and stromal CD8+ T-cell densities in the tumor center compartment that translates spatial densities of tumor-infiltrating CD8+ T cells into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. The consideration of the intratumoral tumor center compartment allows immune phenotyping in the clinically highly relevant setting of metastatic lesions, even if the invasive margin compartment is not captured in biopsy material. Nature Publishing Group US 2021-08-26 2021 /pmc/articles/PMC8590976/ /pubmed/34446805 http://dx.doi.org/10.1038/s41374-021-00653-y Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sobottka, Bettina
Nowak, Marta
Frei, Anja Laura
Haberecker, Martina
Merki, Samuel
Levesque, Mitchell P.
Dummer, Reinhard
Moch, Holger
Koelzer, Viktor Hendrik
Establishing standardized immune phenotyping of metastatic melanoma by digital pathology
title Establishing standardized immune phenotyping of metastatic melanoma by digital pathology
title_full Establishing standardized immune phenotyping of metastatic melanoma by digital pathology
title_fullStr Establishing standardized immune phenotyping of metastatic melanoma by digital pathology
title_full_unstemmed Establishing standardized immune phenotyping of metastatic melanoma by digital pathology
title_short Establishing standardized immune phenotyping of metastatic melanoma by digital pathology
title_sort establishing standardized immune phenotyping of metastatic melanoma by digital pathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590976/
https://www.ncbi.nlm.nih.gov/pubmed/34446805
http://dx.doi.org/10.1038/s41374-021-00653-y
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