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

Lilija Aprupe; Geert Litjens; Titus J Brinker; Jeroen van der Laak; Niels Grabe

doi:10.7717/peerj.6335

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

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

Authors

Lilija Aprupe^{1

2}, Geert Litjens^{3

4}, Titus J Brinker⁵, Jeroen van der Laak³, Niels Grabe^{1

2

4}

Affiliations

¹ Hamamatsu Tissue Imaging and Analysis (TIGA) Center, BioQuant, Heidelberg University, Heidelberg, Germany.
² Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.
³ Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ Steinbeis Center for Medical Systems Biology (STCMSB), Heidelberg, Germany.
⁵ Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.

Abstract

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.

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

Grants and funding

This work was supported by a postdoctoral fellowship for Geert Litjens from the Alexander von Humboldt Foundation. Lilija Aprupe was supported by University Hospital Heidelberg during a time of conducting experiments. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.