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Treg-cell depletion...
Treg-cell depletion promotes chemokine production and accumulation of CXCR3(+) conventional T cells in intestinal tumors.
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- Akeus, Paulina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Langenes, Veronica (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Kristensen, Jonas (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- von Mentzer, Astrid, 1983 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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Sparwasser, Tim (author)
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- Raghavan, Sukanya, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Quiding-Järbrink, Marianne, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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(creator_code:org_t)
- 2015-04-14
- 2015
- English.
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In: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 45:6, s. 1654-66
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Abstract
Subject headings
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- Colorectal cancer (CRC) is one of the most prevalent tumor types worldwide and tumor-infiltrating T cells are crucial for anti-tumor immunity. We previously demonstrated that Treg cells from CRC patients inhibit transendothelial migration of conventional T cells. However, it remains unclear if local Treg cells affect lymphocyte migration into colonic tumors. By breeding APC(Min/+) mice with depletion of regulatory T cells mice, expressing the diphtheria toxin receptor under the control of the FoxP3 promoter, we were able to selectively deplete Treg cells in tumor-bearing mice, and investigate the impact of these cells on the infiltration of conventional T cells into intestinal tumors. Short-term Treg-cell depletion led to a substantial increase in the frequencies of T cells in the tumors, attributed by both increased infiltration and proliferation of T cells in the Treg-cell-depleted tumors. We also demonstrate a selective increase of the chemokines CXCL9 and CXCL10 in Treg-cell-depleted tumors, which were accompanied by accumulation of CXCR3(+) T cells, and increased IFN-γ mRNA expression. In conclusion, Treg-cell depletion increases the accumulation of conventional T cells in intestinal tumors, and targeting Treg cells could be a possible anti-tumor immunotherapy, which not only affects T-cell effector functions, but also their recruitment to tumors.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Adenomatous Polyposis Coli Protein
- metabolism
- Animals
- Cell Adhesion Molecules
- metabolism
- Chemokines
- biosynthesis
- Chemotaxis
- immunology
- Colorectal Neoplasms
- immunology
- metabolism
- Cytokines
- biosynthesis
- Disease Models
- Animal
- Female
- Intestinal Mucosa
- immunology
- metabolism
- Lymphocyte Activation
- immunology
- Lymphocyte Depletion
- Lymphocytes
- Tumor-Infiltrating
- immunology
- metabolism
- Mice
- Phenotype
- Receptors
- CXCR3
- metabolism
- Receptors
- Chemokine
- metabolism
- T-Lymphocyte Subsets
- immunology
- metabolism
- T-Lymphocytes
- Regulatory
- immunology
- Th1 Cells
- immunology
- metabolism
- Vascular Cell Adhesion Molecule-1
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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