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Regulatory T cells ...
Regulatory T cells specifically suppress conventional CD8 alpha beta T cells in intestinal tumors of APC(Min/+) mice
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- Szeponik, Louis (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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- 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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- Rodin, William, 1994 (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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- 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)
- 2020-03-17
- 2020
- English.
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In: Cancer Immunology, Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 69, s. 1279-1292
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https://doi.org/10.1...
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Abstract
Subject headings
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- The presence of activated T cells in colorectal cancer tissues is a strong predictor of patient survival. Our previous studies have shown that regulatory T cells (Treg) are able to reduce T cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo in the murine APC(Min/+) model for microsatellite stable intestinal tumors. In this study, we investigated the effect of Treg depletion on the density and effector functions of different TCR alpha beta(+) and TCR gamma delta(+) T cell populations in intestinal tumors. We used the APC(Min/+)\DEREG mouse model, which harbor a diphtheria toxin receptor under the control of the FOXP3 promoter, to deplete Treg in tumor bearing mice. We found that the density of conventional TCR alpha beta(+)CD8 alpha beta(+) T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCR alpha beta(+)CD8 alpha beta(+) T cells showed increased proliferation and activation as well as increased Granzyme B and IFN-gamma production in Treg-depleted tumors. In sharp contrast, the densities and effector functions of TCR alpha beta(+)CD8 alpha alpha(+) T cells and TCR gamma delta(+) T cells remained unchanged by Treg depletion. We also documented a distinct population of IL-17A(+)TNF(+) TCR gamma delta(+)CD8(-) T cells in tumors, which were not affected by Treg depletion. We conclude that Treg depletion affects only conventional TCR alpha beta(+)CD8 alpha beta(+) T cells in intestinal tumors, while unconventional T cells and T cells in unaffected tissue are not altered. Immunotherapies aimed at depleting Treg from tumors may thus be a viable option for reinvigoration of conventional cytotoxic T cells with a Th1 cytokine profile.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- Regulatory T cells
- APCmin
- Colon cancer
- Tumor-infiltrating
- lymphocytes
- Anti-tumor immunity
- chemokine production
- colon-cancer
- accumulation
- promote
- gamma
- angiogenesis
- mechanisms
- landscape
- depletion
- responses
- Oncology
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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