Abstract
The effect of cancer immunotherapy on the endogenous immune response against tumors is largely unknown. Therefore, we studied immune responses against murine tumors expressing the glycoprotein (GP) and/or nucleoprotein of lymphocytic choriomeningitis virus (LCMV) with or without adoptive T-cell therapy. In nontreated animals, CTLs specific for different epitopes as well as LCMV-GP-specific antibodies contributed to tumor surveillance. Adoptive immunotherapy with monoclonal CTLs specific for LCMV-gp33 impaired the endogenous tumor-specific antibody and CTL response by targeting antigen cross-presenting cells. As a consequence and in contrast to expectations, immunotherapy enhanced tumor growth. Thus, for certain immunogenic tumors, a reduction of tumor-specific B- and T-cell responses and enhanced tumor growth may be an unwanted consequence of adoptive immunotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Chromium / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Epitopes, T-Lymphocyte / immunology
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Fibrosarcoma / immunology
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Fibrosarcoma / therapy*
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Flow Cytometry
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Glycoproteins / immunology
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Glycoproteins / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology
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Humans
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Immunotherapy, Adoptive / methods*
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Interferon-gamma / metabolism
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Lymphocytes, Tumor-Infiltrating / immunology
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Melanoma, Experimental / immunology
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Melanoma, Experimental / therapy*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Nucleoproteins / immunology
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Nucleoproteins / metabolism
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / transplantation*
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T-Lymphocytes, Cytotoxic / immunology
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Viral Proteins / immunology
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Viral Proteins / metabolism
Substances
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Epitopes, T-Lymphocyte
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Glycoproteins
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Homeodomain Proteins
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Nucleoproteins
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Peptide Fragments
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Viral Proteins
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nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus
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Chromium
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RAG-1 protein
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Interferon-gamma