Abstract
IL-7 is known for its role in lymphopoiesis and T-cell homeostasis. In addition, its capacity to augment the immune response to weak or low affinity antigens makes it an ideal candidate to evaluate in combination with a GM-CSF-secreting tumor cell immunotherapy, which has been shown to elicit broad humoral and cellular immune responses. The studies reported here show that IL-7, when combined with a GM-CSF-secreting tumor cell immunotherapy, significantly prolonged the survival of tumor-bearing mice. The enhanced anti-tumor protection correlated with an increased number of activated dendritic cells (DC) and T cells in lymphoid tissues, such as the draining lymph nodes (DLN) and spleen. Moreover, an increased number of activated effector T cells were found in the tumor microenvironment, correlating with a more potent systemic tumor-specific T-cell response than each monotherapy alone. Taken together, these studies demonstrate that IL-7 augments the anti-tumor response of a GM-CSF-secreting tumor cell immunotherapy in preclinical models.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Adjuvants, Immunologic / therapeutic use
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Animals
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CD11c Antigen / analysis
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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Cancer Vaccines / immunology
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Cancer Vaccines / therapeutic use*
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Cell Count
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Cell Line, Tumor
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Female
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
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Interferon-gamma / analysis
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Interleukin-7 / genetics
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Interleukin-7 / pharmacology
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Interleukin-7 / therapeutic use*
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Lymphocyte Activation / drug effects
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Lymphocytes / cytology
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Lymphocytes / drug effects
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Lymphocytes / immunology
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Lysosomal-Associated Membrane Protein 1 / analysis
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology
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Melanoma, Experimental / therapy*
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Membrane Glycoproteins / analysis
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Recombinant Proteins / pharmacology
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Recombinant Proteins / therapeutic use
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Survival Analysis
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gp100 Melanoma Antigen
Substances
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Adjuvants, Immunologic
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CD11c Antigen
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Cancer Vaccines
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IL7 protein, human
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Interleukin-7
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Lysosomal-Associated Membrane Protein 1
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Membrane Glycoproteins
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PMEL protein, human
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Pmel protein, mouse
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Recombinant Proteins
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gp100 Melanoma Antigen
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor