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    Pan-tumor T-lymphocyte detection using deep neural networks:
    recommendations for transfer learning in immunohistochemistry (2023)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Wilm, Frauke
    Ihling, Christian
    Méhes, Gábor
    Terracciano, Luigi
    Puget, Chloé (WE 12)
    Klopfleisch, Robert (WE 12)
    Schüffler, Peter
    Aubreville, Marc
    Maier, Andreas
    Mrowiec, Thomas
    Breininger, Katharina
    Quelle
    Journal of pathology informatics : JPI
    Bandzählung: 14
    Seiten: Artikel 100301
    ISSN: 2153-3539
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://www.sciencedirect.com/science/article/pii/S2153353923001153
    DOI: 10.1016/j.jpi.2023.100301
    Pubmed: 36994311
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    14163 Berlin
    +49 30 838 62450
    pathologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    The success of immuno-oncology treatments promises long-term cancer remission for an increasing number of patients. The response to checkpoint inhibitor drugs has shown a correlation with the presence of immune cells in the tumor and tumor microenvironment. An in-depth understanding of the spatial localization of immune cells is therefore critical for understanding the tumor's immune landscape and predicting drug response. Computer-aided systems are well suited for efficiently quantifying immune cells in their spatial context. Conventional image analysis approaches are often based on color features and therefore require a high level of manual interaction. More robust image analysis methods based on deep learning are expected to decrease this reliance on human interaction and improve the reproducibility of immune cell scoring. However, these methods require sufficient training data and previous work has reported low robustness of these algorithms when they are tested on out-of-distribution data from different pathology labs or samples from different organs. In this work, we used a new image analysis pipeline to explicitly evaluate the robustness of marker-labeled lymphocyte quantification algorithms depending on the number of training samples before and after being transferred to a new tumor indication. For these experiments, we adapted the RetinaNet architecture for the task of T-lymphocyte detection and employed transfer learning to bridge the domain gap between tumor indications and reduce the annotation costs for unseen domains. On our test set, we achieved human-level performance for almost all tumor indications with an average precision of 0.74 in-domain and 0.72-0.74 cross-domain. From our results, we derive recommendations for model development regarding annotation extent, training sample selection, and label extraction for the development of robust algorithms for immune cell scoring. By extending the task of marker-labeled lymphocyte quantification to a multi-class detection task, the pre-requisite for subsequent analyses, e.g., distinguishing lymphocytes in the tumor stroma from tumor-infiltrating lymphocytes, is met.