Abstract
Neoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. Here, we describe a system to introduce exogenous antigens into genetically engineered mouse lung cancers to mimic tumor neoantigens. We show that endogenous T cells respond to and infiltrate tumors, significantly delaying malignant progression. Despite continued antigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. Transplantation of cell lines derived from these lung tumors or prophylactic vaccination against the autochthonous tumors, however, results in rapid tumor eradication or selection of tumors that lose antigen expression. These results provide insight into the dynamic nature of the immune response to naturally arising tumors.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / immunology
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma of Lung
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Adoptive Transfer
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Animals
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Antigen Presentation / immunology
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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Antigens, Neoplasm / metabolism
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Antigens, Surface / metabolism
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Apoptosis / immunology
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Apoptosis Regulatory Proteins / metabolism
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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CD3 Complex / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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Cancer Vaccines / immunology
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Cell Count
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Cell Proliferation
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Cytokines / metabolism
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Genetic Vectors / administration & dosage
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Genetic Vectors / genetics
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Graft Rejection / immunology
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Graft Rejection / pathology
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Histocompatibility Antigens Class I / metabolism
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Humans
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Immunity, Cellular / immunology*
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Interleukin-7 Receptor alpha Subunit / metabolism
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Kaplan-Meier Estimate
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Lentivirus / genetics
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Lentivirus / immunology
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Lung / immunology
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Lung / pathology
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Lung Neoplasms / immunology
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Oligopeptides / genetics
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Oligopeptides / immunology
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Ovalbumin / genetics
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Ovalbumin / immunology
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Programmed Cell Death 1 Receptor
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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T-Lymphocytes / transplantation
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Time Factors
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Transplantation, Isogeneic / immunology
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Transplantation, Isogeneic / pathology
Substances
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Antigens, Neoplasm
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Antigens, Surface
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Apoptosis Regulatory Proteins
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CD3 Complex
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Cancer Vaccines
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Cytokines
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Histocompatibility Antigens Class I
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Interleukin-7 Receptor alpha Subunit
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OVA 323-339
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OVA-8
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Oligopeptides
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Pdcd1 protein, mouse
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Peptide Fragments
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Programmed Cell Death 1 Receptor
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superagonist SIYR
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Ovalbumin