Abstract 1184: Comprehensive analysis with interactive exploration of immune response signatures in 10,000 tumor samples
Authors: Thorsson Vesteinn , Gibbs David L. , Disis Mary L. , Demicco Elizabeth G. , Lazar Alexander J. , Serody Jonathan S. , Eddy James A. , Shmulevich Ilya , Guinney Justin , Vincent Benjamin G. 
Published: August 2019

Abstract
In recent years, analysis of cancer genomics data using methods of immunogenomics has yielded valuable insight into how cancer cells interact with immune cells in the tumor microenvironment. A recent analysis of the multiple molecular platforms by The Cancer Genome Atlas (TCGA) of over 10,000 tumors comprising 33 cancer types identified six immune subtypes, spanning multiple tumor types, that are characterized by differences in: macrophage vs. lymphocyte signatures; Th1:Th2 cell ratio; extent of intratumoral heterogeneity; aneuploidy; extent of neoantigen load; signatures of cell proliferation; expression of immunomodulatory genes; and disease outcome [1]. Particular driver mutations correlate with variation in leukocyte levels across all cancers or with the fraction of individual immune cell types. Intracellular and extracellular networks (involving transcription, microRNAs, copy number and epigenetic processes) are predicted to play a role in establishing the observed tumor-immune cell interactions, both across and within immune subtypes. Additionally, machine learning methods have been applied to H&E images to extract information on which tissue regions contain tumor infiltrating lymphocytes (TILs), yielding TIL maps of whole slide images from digital pathology[2]. Spatial patterns of TILs are associated with a variety of genomic alterations, including cancer subtypes.
The CRI iAtlas (www.cri-iatlas.org) is a cloud-based platform for data exploration and discovery, allowing researchers to study TCGA immune response characterizations, and the relationships among them in individual tumor types, tumor subtypes, and immune subtypes. iAtlas supports the adaptive exploration of correlations within the cellularity of the tumor microenvironment, immune expression signatures, tumor mutation burden, cancer driver mutations, adaptive cell clonality, patient survival, and expression of key immunomodulators. iAtlas was launched in April 2018, and has since been expanded to include new capabilities such as (1) user-defined loading of cohorts, (2) a tool for classifying expression data into immune subtypes, (3) integration of TIL mapping from digital pathology images, and (4) addition of annotated genomics datasets from immunotherapy clinical trials as comparative data sources. As the resource evolves, we expect that the CRI iAtlas will help to accelerate discovery and improve patient outcomes by providing researchers greater access to immunogenomics data to better understand the immunological characteristics of the tumor microenvironment and its potential impact on patient responses to immunotherapy.
[1] Thorsson, V, et al., The Immune Landscape of Cancer; Immunity 48, p812 - 830.e14 (2018)
[2] Saltz, J et al. Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images; Cell Reports 23 pp.181-193.e7 (2018)
Citation Format: Vesteinn Thorsson, David L. Gibbs, Mary L. Disis, Elizabeth G. Demicco, Alexander J. Lazar, Jonathan S. Serody, James A. Eddy, Ilya Shmulevich, Justin Guinney, Benjamin G. Vincent. Comprehensive analysis with interactive exploration of immune response signatures in 10,000 tumor samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1184.