title: Modeling putative therapeutic implications of exosome exchange between tumor and immune cells.
abstract: Development of effective strategies to mobilize the immune system as a therapeutic modality in cancer necessitates a better understanding of the contribution of the tumor microenvironment to the complex interplay between cancer cells and the immune response. Recently, effort has been directed at unraveling the functional role of exosomes and their cargo of messengers in this interplay. Exosomes are small vesicles (30-200 nm) that mediate local and long-range communication through the horizontal transfer of information, such as combinations of proteins, mRNAs and microRNAs. Here, we develop a tractable theoretical framework to study the putative role of exosome-mediated cell-cell communication in the cancer-immunity interplay. We reduce the complex interplay into a generic model whose three components are cancer cells, dendritic cells (consisting of precursor, immature, and mature types), and killer cells (consisting of cytotoxic T cells, helper T cells, effector B cells, and natural killer cells). The framework also incorporates the effects of exosome exchange on enhancement/reduction of cell maturation, proliferation, apoptosis, immune recognition, and activation/inhibition. We reveal tristability-possible existence of three cancer states: a low cancer load with intermediate immune level state, an intermediate cancer load with high immune level state, and a high cancer load with low immune-level state, and establish the corresponding effective landscape for the cancer-immunity network. We illustrate how the framework can contribute to the design and assessments of combination therapies.
authors.affiliation: Center for Theoretical Biological Physics.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Lu
authors.affiliation: Center for Theoretical Biological Physics, Chemistry, and.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, University of Texas MD Anderson Cancer Center, Houston, TX 77030; and.
authors.forename: Samir M
authors.initials: SM
authors.lastname: Hanash
authors.affiliation: Center for Theoretical Biological Physics, Chemistry, and Departments of Physics and Astronomy, Biosciences, Rice University, Houston, TX 77005-1827; jonuchic@rice.edu eshelbj@gmail.com.
authors.forename: José N
authors.initials: JN
authors.lastname: Onuchic
authors.affiliation: Center for Theoretical Biological Physics, Biosciences, Rice University, Houston, TX 77005-1827; School of Physics and Astronomy and The Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 69978, Israel jonuchic@rice.edu eshelbj@gmail.com.
authors.forename: Eshel
authors.initials: E
authors.lastname: Ben-Jacob
mesh_terms: D000465:Algorithms; D000818:Animals; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D055354:Exosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007109:Immunity / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
keywords: cancer exosomes; cancer landscape; cancer therapy; computational modeling; exosome communication