Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoires

Abstract The immune system’s defense abilities rely on the diversity of T and B lymphocytes. T Cell Receptors (TCRs) are generated through V(D)J recombination, where distinct genetic elements combine and undergo modifications, creating extensive variability. In breast cancer, the most frequently dia...

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Main Authors: Miriam Zuckerbrot-Schuldenfrei, Ari Raphael, Alona Zilberberg, Sol Efroni
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Systems Biology and Applications
Online Access:https://doi.org/10.1038/s41540-025-00573-3
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author Miriam Zuckerbrot-Schuldenfrei
Ari Raphael
Alona Zilberberg
Sol Efroni
author_facet Miriam Zuckerbrot-Schuldenfrei
Ari Raphael
Alona Zilberberg
Sol Efroni
author_sort Miriam Zuckerbrot-Schuldenfrei
collection DOAJ
description Abstract The immune system’s defense abilities rely on the diversity of T and B lymphocytes. T Cell Receptors (TCRs) are generated through V(D)J recombination, where distinct genetic elements combine and undergo modifications, creating extensive variability. In breast cancer, the most frequently diagnosed cancer in women, early detection sometimes helps with highly effective and potentially curative treatment. The TCR repertoire may provide information about tumor status. To test this, we investigated the peripheral blood TCR repertoire and its association with tumor status. We collected blood samples from 98 women, including patients and healthy donors. Following TCR profiling, machine learning of these data was able to show an association between TCR profiles and breast cancer presence or absence with high accuracy (average AUC of 0.96). Our findings imply the immune system retains tumor-relevant, TCR-related, signals detectable in blood. This information could potentially benefit future derivatives from this knowledge, either in the field of detection or treatment.
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institution Kabale University
issn 2056-7189
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publishDate 2025-08-01
publisher Nature Portfolio
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series npj Systems Biology and Applications
spelling doaj-art-be7224952fd14f9fb5a8ce21d9a69f7e2025-08-20T04:03:07ZengNature Portfolionpj Systems Biology and Applications2056-71892025-08-011111810.1038/s41540-025-00573-3Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoiresMiriam Zuckerbrot-Schuldenfrei0Ari Raphael1Alona Zilberberg2Sol Efroni3The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan UniversityDavidoff cancer center, Rabin medical center. Faculty of Medical and Health sciences, Tel-Aviv UniversityThe Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan UniversityThe Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan UniversityAbstract The immune system’s defense abilities rely on the diversity of T and B lymphocytes. T Cell Receptors (TCRs) are generated through V(D)J recombination, where distinct genetic elements combine and undergo modifications, creating extensive variability. In breast cancer, the most frequently diagnosed cancer in women, early detection sometimes helps with highly effective and potentially curative treatment. The TCR repertoire may provide information about tumor status. To test this, we investigated the peripheral blood TCR repertoire and its association with tumor status. We collected blood samples from 98 women, including patients and healthy donors. Following TCR profiling, machine learning of these data was able to show an association between TCR profiles and breast cancer presence or absence with high accuracy (average AUC of 0.96). Our findings imply the immune system retains tumor-relevant, TCR-related, signals detectable in blood. This information could potentially benefit future derivatives from this knowledge, either in the field of detection or treatment.https://doi.org/10.1038/s41540-025-00573-3
spellingShingle Miriam Zuckerbrot-Schuldenfrei
Ari Raphael
Alona Zilberberg
Sol Efroni
Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoires
npj Systems Biology and Applications
title Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoires
title_full Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoires
title_fullStr Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoires
title_full_unstemmed Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoires
title_short Breast cancer is detectable from peripheral blood using machine learning over T cell receptor repertoires
title_sort breast cancer is detectable from peripheral blood using machine learning over t cell receptor repertoires
url https://doi.org/10.1038/s41540-025-00573-3
work_keys_str_mv AT miriamzuckerbrotschuldenfrei breastcancerisdetectablefromperipheralbloodusingmachinelearningovertcellreceptorrepertoires
AT ariraphael breastcancerisdetectablefromperipheralbloodusingmachinelearningovertcellreceptorrepertoires
AT alonazilberberg breastcancerisdetectablefromperipheralbloodusingmachinelearningovertcellreceptorrepertoires
AT solefroni breastcancerisdetectablefromperipheralbloodusingmachinelearningovertcellreceptorrepertoires