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PeerJ. 2019 Apr 10;7:e6335. doi: 10.7717/peerj.6335. eCollection 2019.

Robust and accurate quantification of biomarkers of immune cells in lung cancer micro-environment using deep convolutional neural networks.

Author information

Hamamatsu Tissue Imaging and Analysis (TIGA) Center, BioQuant, Heidelberg University, Heidelberg, Germany.
Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
Steinbeis Center for Medical Systems Biology (STCMSB), Heidelberg, Germany.
Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.


Recent years have seen a growing awareness of the role the immune system plays in successful cancer treatment, especially in novel therapies like immunotherapy. The characterization of the immunological composition of tumors and their micro-environment is thus becoming a necessity. In this paper we introduce a deep learning-based immune cell detection and quantification method, which is based on supervised learning, i.e., the input data for training comprises labeled images. Our approach objectively deals with staining variation and staining artifacts in immunohistochemically stained lung cancer tissue and is as precise as humans. This is evidenced by the low cell count difference to humans of 0.033 cells on average. This method, which is based on convolutional neural networks, has the potential to provide a new quantitative basis for research on immunotherapy.


Biomarker quantification; Cancer micro-environment; Deep learning; Immune cells; Lung cancer

Conflict of interest statement

Jeroen van der Laak is a member of the scientific advisory boards of Philips Digital Pathology (Best, Netherlands) and ContextVision (Linkoping, Sweden). Titus J. Brinker would like to declare that he is the owner of Smart Health Heidelberg GmbH (Handschuhsheimer Landstr. 9/1, 69120 Heidelberg), a technology company involved in the development of medical apps. Geert Litjens received research funding from Philips Digital Pathology Solutions (Best, the Netherlands) and has a consultancy role for Novartis (Basel, Switzerland). He received research grants from the Dutch Cancer Society (KUN 2015-7970), from Netherlands Organization for Scientific Research (NWO) (project number 016.186.152) and from Stichting IT Projecten (project PATHOLOGIE 2). Lilija Aprupe, and Niels Grabe declare that they have no competing interests.

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