Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images.

Journal: Cell reports
Published Date:

Abstract

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment.

Authors

  • Joel Saltz
    Department of Biomedical Informatics, Stony Brook University, Stony Brook, New York.
  • Rajarsi Gupta
    Department of Biomedical Informatics, Stony Brook Medicine, Stony Brook, NY 11794, USA; Department of Pathology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
  • Le Hou
    Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.
  • Tahsin Kurc
    Department of Biomedical Informatics, Stony Brook Medicine, Stony Brook, NY 11794, USA.
  • Pankaj Singh
    Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Vu Nguyen
    Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.
  • Dimitris Samaras
    Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.
  • Kenneth R Shroyer
    Department of Pathology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
  • Tianhao Zhao
    Department of Pathology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
  • Rebecca Batiste
    Department of Pathology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
  • John Van Arnam
    Department of Pathology and Laboratory Medicine, Perelman School at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Ilya Shmulevich
    Institute for Systems Biology, Seattle, WA 98109, USA.
  • Arvind U K Rao
    Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Alexander J Lazar
    The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ashish Sharma
    Department of Biomedical Informatics, Emory University, Atlanta, GA 30322, USA.
  • Vésteinn Thorsson
    Institute for Systems Biology, Seattle, WA 98109, USA. Electronic address: vesteinn.thorsson@systemsbiology.org.