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Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response
While immune checkpoint–based immunotherapy (ICI) shows promising clinical results in patients with cancer, only a subset of patients responds favorably. Response to ICI is dictated by complex networks of cellular interactions between malignant and nonmalignant cells. Although insights into the mech...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478533/ https://www.ncbi.nlm.nih.gov/pubmed/35834277 http://dx.doi.org/10.1158/0008-5472.CAN-22-0363 |
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author | Antoranz, Asier Van Herck, Yannick Bolognesi, Maddalena M. Lynch, Seodhna M. Rahman, Arman Gallagher, William M. Boecxstaens, Veerle Marine, Jean-Christophe Cattoretti, Giorgio van den Oord, Joost J. De Smet, Frederik Bechter, Oliver Bosisio, Francesca M. |
author_facet | Antoranz, Asier Van Herck, Yannick Bolognesi, Maddalena M. Lynch, Seodhna M. Rahman, Arman Gallagher, William M. Boecxstaens, Veerle Marine, Jean-Christophe Cattoretti, Giorgio van den Oord, Joost J. De Smet, Frederik Bechter, Oliver Bosisio, Francesca M. |
author_sort | Antoranz, Asier |
collection | PubMed |
description | While immune checkpoint–based immunotherapy (ICI) shows promising clinical results in patients with cancer, only a subset of patients responds favorably. Response to ICI is dictated by complex networks of cellular interactions between malignant and nonmalignant cells. Although insights into the mechanisms that modulate the pivotal antitumoral activity of cytotoxic T cells (Tcy) have recently been gained, much of what has been learned is based on single-cell analyses of dissociated tumor samples, resulting in a lack of critical information about the spatial distribution of relevant cell types. Here, we used multiplexed IHC to spatially characterize the immune landscape of metastatic melanoma from responders and nonresponders to ICI. Such high-dimensional pathology maps showed that Tcy gradually evolve toward an exhausted phenotype as they approach and infiltrate the tumor. Moreover, a key cellular interaction network functionally linked Tcy and PD-L1(+) macrophages. Mapping the respective spatial distributions of these two cell populations predicted response to anti-PD-1 immunotherapy with high confidence. These results suggest that baseline measurements of the spatial context should be integrated in the design of predictive biomarkers to identify patients likely to benefit from ICI. SIGNIFICANCE: This study shows that spatial characterization can address the challenge of finding efficient biomarkers, revealing that localization of macrophages and T cells in melanoma predicts patient response to ICI. See related commentary by Smalley and Smalley, p. 3198 |
format | Online Article Text |
id | pubmed-9478533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-94785332023-01-05 Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response Antoranz, Asier Van Herck, Yannick Bolognesi, Maddalena M. Lynch, Seodhna M. Rahman, Arman Gallagher, William M. Boecxstaens, Veerle Marine, Jean-Christophe Cattoretti, Giorgio van den Oord, Joost J. De Smet, Frederik Bechter, Oliver Bosisio, Francesca M. Cancer Res Tumor Biology and Immunology While immune checkpoint–based immunotherapy (ICI) shows promising clinical results in patients with cancer, only a subset of patients responds favorably. Response to ICI is dictated by complex networks of cellular interactions between malignant and nonmalignant cells. Although insights into the mechanisms that modulate the pivotal antitumoral activity of cytotoxic T cells (Tcy) have recently been gained, much of what has been learned is based on single-cell analyses of dissociated tumor samples, resulting in a lack of critical information about the spatial distribution of relevant cell types. Here, we used multiplexed IHC to spatially characterize the immune landscape of metastatic melanoma from responders and nonresponders to ICI. Such high-dimensional pathology maps showed that Tcy gradually evolve toward an exhausted phenotype as they approach and infiltrate the tumor. Moreover, a key cellular interaction network functionally linked Tcy and PD-L1(+) macrophages. Mapping the respective spatial distributions of these two cell populations predicted response to anti-PD-1 immunotherapy with high confidence. These results suggest that baseline measurements of the spatial context should be integrated in the design of predictive biomarkers to identify patients likely to benefit from ICI. SIGNIFICANCE: This study shows that spatial characterization can address the challenge of finding efficient biomarkers, revealing that localization of macrophages and T cells in melanoma predicts patient response to ICI. See related commentary by Smalley and Smalley, p. 3198 American Association for Cancer Research 2022-09-16 2022-07-14 /pmc/articles/PMC9478533/ /pubmed/35834277 http://dx.doi.org/10.1158/0008-5472.CAN-22-0363 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Tumor Biology and Immunology Antoranz, Asier Van Herck, Yannick Bolognesi, Maddalena M. Lynch, Seodhna M. Rahman, Arman Gallagher, William M. Boecxstaens, Veerle Marine, Jean-Christophe Cattoretti, Giorgio van den Oord, Joost J. De Smet, Frederik Bechter, Oliver Bosisio, Francesca M. Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response |
title | Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response |
title_full | Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response |
title_fullStr | Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response |
title_full_unstemmed | Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response |
title_short | Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response |
title_sort | mapping the immune landscape in metastatic melanoma reveals localized cell–cell interactions that predict immunotherapy response |
topic | Tumor Biology and Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478533/ https://www.ncbi.nlm.nih.gov/pubmed/35834277 http://dx.doi.org/10.1158/0008-5472.CAN-22-0363 |
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