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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Bibliographic Details
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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Summary: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.
ISSN:2056-7189