DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Learning-accelerated discovery of immune-tumour interactions

Journal Article · · Molecular Systems Design & Engineering
DOI: https://doi.org/10.1039/c9me00036d · OSTI ID:1574308

We present an integrated framework for enabling dynamic exploration of design spaces for cancer immunotherapies with detailed dynamical simulation models on high-performance computing resources. Our framework combines PhysiCell, an open source agent-based simulation platform for cancer and other multicellular systems, and EMEWS, an open source platform for extreme-scale model exploration. We build an agent-based model of immunosurveillance against heterogeneous tumours, which includes spatial dynamics of stochastic tumour–immune contact interactions. We implement active learning and genetic algorithms using high-performance computing workflows to adaptively sample the model parameter space and iteratively discover optimal cancer regression regions within biological and clinical constraints.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Science Foundation (NSF); National Institutes of Health (NIH); USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1574308
Journal Information:
Molecular Systems Design & Engineering, Vol. 4, Issue 4; ISSN 2058-9689
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

References (79)

Genetically modified T cells in cancer therapy: opportunities and challenges journal April 2015
Mathematical Modeling in Immunotherapy of Cancer: Personalizing Clinical Trials journal January 2012
Extension of in vivo half-life of biologically active molecules by XTEN protein polymers journal October 2016
Extreme-Scale Dynamic Exploration of a Distributed Agent-Based Model With the EMEWS Framework journal September 2018
Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance preprint January 2013
Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures journal November 2017
Mathematical and computational models of immune-receptor signalling journal June 2004
Exhaustion of cytotoxic T cells during adoptive immunotherapy of virus carrier mice can be prevented by B cells or CD4+ T cells journal February 2002
Addressing current challenges in cancer immunotherapy with mathematical and computational modelling journal June 2017
Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead journal October 2017
When Seeing Isn't Believing: How Math Can Guide Our Interpretation of Measurements and Experiments journal August 2017
BioFVM: an efficient, parallelized diffusive transport solver for 3-D biological simulations journal December 2015
Dynamic analysis of immune and cancer cell interactions at single cell level in microfluidic droplets journal September 2016
Proteome-Wide Measurement of Protein Half-Lives and Translation Rates in Vasopressin-Sensitive Collecting Duct Cells journal September 2013
Exploiting evolutionary principles to prolong tumor control in preclinical models of breast cancer journal February 2016
Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence book January 1992
Mathematical modeling of intracellular signaling pathways journal October 2006
libRoadRunner: a high performance SBML simulation and analysis library: Table 1. journal June 2015
Classifying the evolutionary and ecological features of neoplasms journal September 2017
Active Subspaces book January 2015
Strength in Numbers: Visualizing CTL-Mediated Killing In Vivo journal February 2016
T cell migration, search strategies and mechanisms journal February 2016
Analysis of response rate with ANTI PD1/PD-L1 monoclonal antibodies in advanced solid tumors: a meta-analysis of randomized clinical trials journal January 2018
Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance journal August 2013
Practical Heteroscedastic Gaussian Process Modeling for Large Simulation Experiments journal July 2018
Post-translational modification of the interferon-gamma receptor alters its stability and signaling journal October 2017
PhysiBoSS: a multi-scale agent-based modelling framework integrating physical dimension and cell signalling journal August 2018
The Kinematics of Cytotoxic Lymphocytes Influence Their Ability to Kill Target Cells journal May 2014
Decitabine and Vorinostat Cooperate To Sensitize Colon Carcinoma Cells to Fas Ligand-Induced Apoptosis In Vitro and Tumor Suppression In Vivo journal March 2012
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity journal February 2016
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma journal October 2017
Hallmarks of Cancer: The Next Generation journal March 2011
Where to Go: Breaking the Symmetry in Cell Motility journal May 2016
Dynamic analysis of immune and cancer cell interactions at single cell level in microfluidic droplets journal September 2016
A Review of Cell-Based Computational Modeling in Cancer Biology journal November 2019
Cancer immunotherapy in clinical practice��the past, present, and future journal September 2014
Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance preprint January 2013
Mathematical Modeling in Immunotherapy of Cancer: Personalizing Clinical Trials journal January 2012
Hallmarks of Cancer: The Next Generation journal March 2011
Staging the Tumor and Staging the Host: Pretreatment Combined Neutrophil Lymphocyte Ratio and Modified Glasgow Prognostic Score Is Associated with Overall Survival in Patients with Esophagogastric Cancers Undergoing Treatment with Curative Intent journal September 2020
Analysis of response rate with ANTI PD1/PD-L1 monoclonal antibodies in advanced solid tumors: a meta-analysis of randomized clinical trials journal January 2018
Optimizing Cancer Treatment Using Game Theory: A Review journal January 2019
The Kinematics of Cytotoxic Lymphocytes Influence Their Ability to Kill Target Cells journal May 2014
PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems journal February 2018
miRNALoc: predicting miRNA subcellular localizations based on principal component scores of physico-chemical properties and pseudo compositions of di-nucleotides journal September 2020
Exascale design space exploration and co-design journal January 2014
Self-Generated Chemoattractant Gradients: Attractant Depletion Extends the Range and Robustness of Chemotaxis journal March 2016
Closing the Scientific Loop: Bridging Correlation and Causality in the Petaflop Age journal July 2010
The Three Es of Cancer Immunoediting journal April 2004
Treating Cancer by Targeting the Immune System journal August 2010
Natural Innate and Adaptive Immunity to Cancer journal April 2011
Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures journal November 2017
Mathematical and computational models of immune-receptor signalling journal June 2004
Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment journal January 2019
libRoadRunner: a high performance SBML simulation and analysis library: Table 1. journal June 2015
High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow journal December 2018
Abstract 611: PD-1-based combination immunotherapy reinvigorates CD8 + T cells in metastatic pancreatic cancer patients with improved survival conference July 2018
Three-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. journal May 2016
Tumor–stroma interactions journal February 2005
xml2jupyter: Mapping parameters between XML and Jupyter widgets journal July 2019
Decitabine and Vorinostat Cooperate To Sensitize Colon Carcinoma Cells to Fas Ligand-Induced Apoptosis In Vitro and Tumor Suppression In Vivo journal March 2012
Mathematical Modeling and Parameter Estimation of Intracellular Signaling Pathway: Application to LPS-induced NFκB Activation and TNFα Production in Macrophages journal February 2018
Dimensional and temporal controls of three-dimensional cell migration by zyxin and binding partners journal January 2012
T cell migration, search strategies and mechanisms journal February 2016
Dimensional and temporal controls of three-dimensional cell migration by zyxin and binding partners journal January 2012
Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment journal January 2019
Active learning* journal January 2007
BioFVM: an efficient, parallelized diffusive transport solver for 3-D biological simulations journal December 2015
Parallel agent-based simulation with Repast for High Performance Computing journal November 2012
Exascale Computing Technology Challenges book January 2010
Natural Innate and Adaptive Immunity to Cancer journal April 2011
Rethinking Hardware-Software Codesign for Exascale Systems journal November 2011
Tumour surveillance: Missing peptides and MHC molecules journal February 1998
The Three Es of Cancer Immunoediting journal April 2004
Addressing current challenges in cancer immunotherapy with mathematical and computational modeling text January 2017
Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation journal May 2008
Nonlinear modelling of cancer: bridging the gap between cells and tumours journal December 2009
Random Forests journal January 2001
Cancer immunotherapy in clinical practice��the past, present, and future journal September 2014

Cited By (6)