Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study

Abstract Emerging data indicate that genomic alterations can shape immune cell composition in early breast cancer. However, there is a need for complementary imaging and sequencing methods for the quantitative assessment of combined somatic copy number alteration (SCNA) and immune profiling in patho...

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Autores principales:	Ioannis Zerdes, Michele Simonetti, Alexios Matikas, Luuk Harbers, Balazs Acs, Ceren Boyaci, Ning Zhang, Dimitrios Salgkamis, Susanne Agartz, Pablo Moreno-Ruiz, Yalai Bai, David L. Rimm, Johan Hartman, Artur Mezheyeuski, Jonas Bergh, Nicola Crosetto, Theodoros Foukakis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3346ad4f61b5411594a62c963ed56bb4
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spelling	oai:doaj.org-article:3346ad4f61b5411594a62c963ed56bb42021-11-21T12:31:48ZInterplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study10.1038/s41523-021-00352-32374-4677https://doaj.org/article/3346ad4f61b5411594a62c963ed56bb42021-11-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00352-3https://doaj.org/toc/2374-4677Abstract Emerging data indicate that genomic alterations can shape immune cell composition in early breast cancer. However, there is a need for complementary imaging and sequencing methods for the quantitative assessment of combined somatic copy number alteration (SCNA) and immune profiling in pathological samples. Here, we tested the feasibility of three approaches—CUTseq, for high-throughput low-input SCNA profiling, multiplexed fluorescent immunohistochemistry (mfIHC) and digital-image analysis (DIA) for quantitative immuno-profiling- in archival formalin-fixed paraffin-embedded (FFPE) tissue samples from patients enrolled in the randomized SBG-2004-1 phase II trial. CUTseq was able to reproducibly identify amplification and deletion events with a resolution of 100 kb using only 6 ng of DNA extracted from FFPE tissue and pooling together 77 samples into the same sequencing library. In the same samples, mfIHC revealed that CD4 + T-cells and CD68 + macrophages were the most abundant immune cells and they mostly expressed PD-L1 and PD-1. Combined analysis showed that the SCNA burden was inversely associated with lymphocytic infiltration. Our results set the basis for further applications of CUTseq, mfIHC and DIA to larger cohorts of early breast cancer patients.Ioannis ZerdesMichele SimonettiAlexios MatikasLuuk HarbersBalazs AcsCeren BoyaciNing ZhangDimitrios SalgkamisSusanne AgartzPablo Moreno-RuizYalai BaiDavid L. RimmJohan HartmanArtur MezheyeuskiJonas BerghNicola CrosettoTheodoros FoukakisNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ioannis Zerdes Michele Simonetti Alexios Matikas Luuk Harbers Balazs Acs Ceren Boyaci Ning Zhang Dimitrios Salgkamis Susanne Agartz Pablo Moreno-Ruiz Yalai Bai David L. Rimm Johan Hartman Artur Mezheyeuski Jonas Bergh Nicola Crosetto Theodoros Foukakis Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
description	Abstract Emerging data indicate that genomic alterations can shape immune cell composition in early breast cancer. However, there is a need for complementary imaging and sequencing methods for the quantitative assessment of combined somatic copy number alteration (SCNA) and immune profiling in pathological samples. Here, we tested the feasibility of three approaches—CUTseq, for high-throughput low-input SCNA profiling, multiplexed fluorescent immunohistochemistry (mfIHC) and digital-image analysis (DIA) for quantitative immuno-profiling- in archival formalin-fixed paraffin-embedded (FFPE) tissue samples from patients enrolled in the randomized SBG-2004-1 phase II trial. CUTseq was able to reproducibly identify amplification and deletion events with a resolution of 100 kb using only 6 ng of DNA extracted from FFPE tissue and pooling together 77 samples into the same sequencing library. In the same samples, mfIHC revealed that CD4 + T-cells and CD68 + macrophages were the most abundant immune cells and they mostly expressed PD-L1 and PD-1. Combined analysis showed that the SCNA burden was inversely associated with lymphocytic infiltration. Our results set the basis for further applications of CUTseq, mfIHC and DIA to larger cohorts of early breast cancer patients.
format	article
author	Ioannis Zerdes Michele Simonetti Alexios Matikas Luuk Harbers Balazs Acs Ceren Boyaci Ning Zhang Dimitrios Salgkamis Susanne Agartz Pablo Moreno-Ruiz Yalai Bai David L. Rimm Johan Hartman Artur Mezheyeuski Jonas Bergh Nicola Crosetto Theodoros Foukakis
author_facet	Ioannis Zerdes Michele Simonetti Alexios Matikas Luuk Harbers Balazs Acs Ceren Boyaci Ning Zhang Dimitrios Salgkamis Susanne Agartz Pablo Moreno-Ruiz Yalai Bai David L. Rimm Johan Hartman Artur Mezheyeuski Jonas Bergh Nicola Crosetto Theodoros Foukakis
author_sort	Ioannis Zerdes
title	Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
title_short	Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
title_full	Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
title_fullStr	Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
title_full_unstemmed	Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
title_sort	interplay between copy number alterations and immune profiles in the early breast cancer scandinavian breast group 2004-1 randomized phase ii trial: results from a feasibility study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3346ad4f61b5411594a62c963ed56bb4
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Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study

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