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Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response

The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomar...

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Autores principales: Vo, Duong H. T., McGleave, Gerard, Overton, Ian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225330/
https://www.ncbi.nlm.nih.gov/pubmed/35743743
http://dx.doi.org/10.3390/jpm12060958
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author Vo, Duong H. T.
McGleave, Gerard
Overton, Ian M.
author_facet Vo, Duong H. T.
McGleave, Gerard
Overton, Ian M.
author_sort Vo, Duong H. T.
collection PubMed
description The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, ‘immune hot’ status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.
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spelling pubmed-92253302022-06-24 Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response Vo, Duong H. T. McGleave, Gerard Overton, Ian M. J Pers Med Article The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, ‘immune hot’ status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine. MDPI 2022-06-11 /pmc/articles/PMC9225330/ /pubmed/35743743 http://dx.doi.org/10.3390/jpm12060958 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vo, Duong H. T.
McGleave, Gerard
Overton, Ian M.
Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response
title Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response
title_full Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response
title_fullStr Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response
title_full_unstemmed Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response
title_short Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response
title_sort immune cell networks uncover candidate biomarkers of melanoma immunotherapy response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225330/
https://www.ncbi.nlm.nih.gov/pubmed/35743743
http://dx.doi.org/10.3390/jpm12060958
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