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Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines

The endoplasmic reticulum (ER) is a major site of passage for proteins en route to other organelles, to the cell surface, and to the extracellular space. It is also the transport route for peptides generated in the cytosol by the proteasome into the ER for loading onto major histocompatibility compl...

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Autores principales: Graner, Michael W., Lillehei, Kevin O., Katsanis, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285071/
https://www.ncbi.nlm.nih.gov/pubmed/25610811
http://dx.doi.org/10.3389/fonc.2014.00379
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author Graner, Michael W.
Lillehei, Kevin O.
Katsanis, Emmanuel
author_facet Graner, Michael W.
Lillehei, Kevin O.
Katsanis, Emmanuel
author_sort Graner, Michael W.
collection PubMed
description The endoplasmic reticulum (ER) is a major site of passage for proteins en route to other organelles, to the cell surface, and to the extracellular space. It is also the transport route for peptides generated in the cytosol by the proteasome into the ER for loading onto major histocompatibility complex class I (MHC I) molecules for eventual antigen presentation at the cell surface. Chaperones within the ER are critical for many of these processes; however, outside the ER certain of those chaperones may play important and direct roles in immune responses. In some cases, particular ER chaperones have been utilized as vaccines against tumors or infectious disease pathogens when purified from tumor tissue or recombinantly generated and loaded with antigen. In other cases, the cell surface location of ER chaperones has implications for immune responses as well as possible tumor resistance. We have produced heat-shock protein/chaperone protein-based cancer vaccines called “chaperone-rich cell lysate” (CRCL) that are conglomerates of chaperones enriched from solid tumors by an isoelectric focusing technique. These preparations have been effective against numerous murine tumors, as well as in a canine with an advanced lung carcinoma treated with autologous CRCL. We also published extensive proteomic analyses of CRCL prepared from human surgically resected tumor samples. Of note, these preparations contained at least 10 ER chaperones and a number of other residents, along with many other chaperones/heat-shock proteins. Gene ontology and network analyses utilizing these proteins essentially recapitulate the antigen presentation pathways and interconnections. In conjunction with our current knowledge of cell surface/extracellular ER chaperones, these data collectively suggest that a systems-level view may provide insight into the potent immune stimulatory activities of CRCL with an emphasis on the roles of ER components in those processes.
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spelling pubmed-42850712015-01-21 Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines Graner, Michael W. Lillehei, Kevin O. Katsanis, Emmanuel Front Oncol Oncology The endoplasmic reticulum (ER) is a major site of passage for proteins en route to other organelles, to the cell surface, and to the extracellular space. It is also the transport route for peptides generated in the cytosol by the proteasome into the ER for loading onto major histocompatibility complex class I (MHC I) molecules for eventual antigen presentation at the cell surface. Chaperones within the ER are critical for many of these processes; however, outside the ER certain of those chaperones may play important and direct roles in immune responses. In some cases, particular ER chaperones have been utilized as vaccines against tumors or infectious disease pathogens when purified from tumor tissue or recombinantly generated and loaded with antigen. In other cases, the cell surface location of ER chaperones has implications for immune responses as well as possible tumor resistance. We have produced heat-shock protein/chaperone protein-based cancer vaccines called “chaperone-rich cell lysate” (CRCL) that are conglomerates of chaperones enriched from solid tumors by an isoelectric focusing technique. These preparations have been effective against numerous murine tumors, as well as in a canine with an advanced lung carcinoma treated with autologous CRCL. We also published extensive proteomic analyses of CRCL prepared from human surgically resected tumor samples. Of note, these preparations contained at least 10 ER chaperones and a number of other residents, along with many other chaperones/heat-shock proteins. Gene ontology and network analyses utilizing these proteins essentially recapitulate the antigen presentation pathways and interconnections. In conjunction with our current knowledge of cell surface/extracellular ER chaperones, these data collectively suggest that a systems-level view may provide insight into the potent immune stimulatory activities of CRCL with an emphasis on the roles of ER components in those processes. Frontiers Media S.A. 2015-01-06 /pmc/articles/PMC4285071/ /pubmed/25610811 http://dx.doi.org/10.3389/fonc.2014.00379 Text en Copyright © 2015 Graner, Lillehei and Katsanis. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Graner, Michael W.
Lillehei, Kevin O.
Katsanis, Emmanuel
Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines
title Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines
title_full Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines
title_fullStr Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines
title_full_unstemmed Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines
title_short Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines
title_sort endoplasmic reticulum chaperones and their roles in the immunogenicity of cancer vaccines
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285071/
https://www.ncbi.nlm.nih.gov/pubmed/25610811
http://dx.doi.org/10.3389/fonc.2014.00379
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