Abstract
The probability of producing a specific antitumor response should be increased by multiplying the number of T lymphocytes that encounter the malignant cells. We tested this prediction in a murine model, using a recently discovered T-cell chemokine, lymphotactin (Lptn). This chemokine increased tumor cell infiltration with CD4+ lymphocytes but generated little antitumor activity. Coexpression of the T-cell growth factor interleukin-2, however, greatly expanded the T lymphocytes attracted by Lptn, affording protection from the growth of established tumor in a CD4+ and CD8+ T cell-dependent manner. Lesser synergy was seen with GM-CSF. Hence coexpression of a T-cell chemokine and T-cell growth factor potentiates antitumor responses in vivo, suggesting a general strategy to improve cancer immunotherapy.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / immunology
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Chemokines, C*
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Chemotaxis, Leukocyte
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Female
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Fibroblasts / transplantation
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Gene Transfer Techniques*
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Genes, Reporter
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / physiology
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Immunization
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Interleukin-2 / biosynthesis
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Interleukin-2 / genetics
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Interleukin-2 / physiology*
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Lymphocytes, Tumor-Infiltrating / immunology*
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Lymphokines / biosynthesis
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Lymphokines / genetics
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Lymphokines / physiology*
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Lymphoma, B-Cell / immunology*
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Lymphoma, B-Cell / prevention & control
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Lymphoma, B-Cell / therapy
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Mice
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Mice, Inbred BALB C
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Neoplasm Transplantation
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Recombinant Fusion Proteins / metabolism
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Sialoglycoproteins / biosynthesis
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Sialoglycoproteins / genetics
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Sialoglycoproteins / physiology*
Substances
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Chemokines, C
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Interleukin-2
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Lymphokines
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Recombinant Fusion Proteins
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Sialoglycoproteins
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Xcl1 protein, mouse
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lymphotactin
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Granulocyte-Macrophage Colony-Stimulating Factor