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

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 s...

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Bibliographic Details
Published in:NPJ breast cancer 2021-11, Vol.7 (1), p.144-144, Article 144
Main Authors: Zerdes, Ioannis, Simonetti, Michele, Matikas, Alexios, Harbers, Luuk, Acs, Balazs, Boyaci, Ceren, Zhang, Ning, Salgkamis, Dimitrios, Agartz, Susanne, Moreno-Ruiz, Pablo, Bai, Yalai, Rimm, David L., Hartman, Johan, Mezheyeuski, Artur, Bergh, Jonas, Crosetto, Nicola, Foukakis, Theodoros
Format: Article
Language:English
Subjects:
631/67/327
631/67/69
692/4028/67/1347
Automation
Biomarkers
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cell Biology
Feasibility studies
Gene expression
Genomes
Human Genetics
Immunotherapy
Lymphocytes
Medicin och hälsovetenskap
Oncology
Pathology
Tumors
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Summary: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.
ISSN:2374-4677
2374-4677
DOI:10.1038/s41523-021-00352-3