Abstract
Immune evasion within the tumor microenvironment supports malignant growth and is also a major obstacle for successful immunotherapy. Multiple cellular components and soluble factors coordinate to disrupt protective immune responses. Although stromal cells are well-known for their parenchymal supportive roles in cancer establishment and progression, we demonstrate for the first time, to our knowledge, that tumor-derived vascular pericytes negatively influence CD4(+) T cell activation and proliferation, and promote anergy in recall response to Ag by CD4(+)CD44(+) T cells via regulator of G protein signaling 5- and IL-6-dependent pathways. Our data support a new specific role for tumor-derived pericytes in the immune evasion paradigm within the tumor microenvironment and suggest the targeting of these cell populations in the context of successful immunotherapeutics for the treatment of cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Cells / immunology
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CD4-Positive T-Lymphocytes / immunology*
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Cell Line
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Cell Proliferation
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Chemokines / metabolism
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Clonal Anergy / immunology*
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Dendritic Cells / immunology
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Female
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GTP-Binding Proteins / metabolism
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Histocompatibility Antigens Class II / metabolism
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Hyaluronan Receptors / metabolism
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-6 / metabolism
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Neoplasms / immunology*
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Pericytes / metabolism*
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RGS Proteins / genetics
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RGS Proteins / metabolism
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RNA Interference
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RNA, Small Interfering
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Tumor Escape*
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Tumor Microenvironment / immunology
Substances
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Chemokines
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Histocompatibility Antigens Class II
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Hyaluronan Receptors
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Interleukin-6
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RGS Proteins
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RNA, Small Interfering
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Rgs5 protein, mouse
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VCC-1 protein, mouse
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Intercellular Adhesion Molecule-1
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GTP-Binding Proteins