OCT 11, 2017 10:30 AM PDT

Brain Tumor Exosomes in Cancer Immunity: Fat Balls of Immune Confusion

Speaker
  • Associate Professor, Department of Neurosurgery, University of Colorado Denver
    Biography
      Graner is an Associate Professor of Neurosurgery at the University of Colorado Denver, Anschutz Medical Campus (which is actually in Aurora, and he is not an actual neurosurgeon). He received his PhD in Biochemistry at the University of Illinois (working on fruit flies, of all things). He post-doc'd at the University of Arizona in Cell and Molecular Biology (more flies), and then as assorted sub-faculty level positions in Pediatric Oncology (a perfectly logical transition). There he actually used his biochem training to develop an autologous form of anti-cancer vaccines (called "CRCL", it's a long story). Later, he worked at the Tisch Brain Tumor Center at Duke University, leading to his position in Neuro-Oncology at Colorado. He has continued to study cancer immunology, in particular as it relates to the biology of tumor extracellular vesicles (aka exosomes and microvesicles). He is the Research Director and Steering Committee Chair of the Neurosurgery Nervous System Biorepository, and is the President-Elect of the Society for Thermal Medicine, and has numerous dogs and cats.

    Abstract

    Exosomes are nano-scale lipid membrane-enclosed extracellular vesicles that form in the cellular endosomal system but are released outside the cell. These virus-sized “fat balls” (which also contain numerous proteins, nucleic acids, and other metabolites) are capable of extraordinary autocrine/paracrine and endocrine signaling functions on recipient cells that are proximal to, and distal from, the cells of origin. We have studied several areas of tumor-derived exosome impacts on recipient cells, whether those recipients are the tumor cells themselves (brain tumor cells, in this case), immune cells (lymphocytes in particular), and neighboring normal cells (glial cells/astrocytes). The common denominator in all of these cell/tumor exosome interactions is that the outcomes generally benefit the tumor, but that can be dependent on the context. In this talk we will describe our experiences with glioma exosomes 1) as cancer vaccines (immune stimulation!), but also as 2) agents of cancer immunosuppression (as mentioned, context-dependent), and as 3) drivers of inflammatory responses that seem to aid and abet tumor growth (and may turn normal cells into cancer cell progenitors). As opposed to a “unified field theory”, we instead offer the concept that cellular context and timing of arrival determine the downstream effects of glioma exosomes on the cells that encounter those fat balls.


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