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- Szeponik, LouisGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology (author)
Regulatory T cells specifically suppress conventional CD8 alpha beta T cells in intestinal tumors of APC(Min/+) mice
- Article/chapterEnglish2020
Publisher, publication year, extent ...
- 2020-03-17
- Springer Science and Business Media LLC,2020
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- LIBRIS-ID:oai:gup.ub.gu.se/292449
- https://gup.ub.gu.se/publication/292449URI
- https://doi.org/10.1007/s00262-020-02540-9DOI
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- Language:English
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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 and genre
- 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
- 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
Added entries (persons, corporate bodies, meetings, titles ...)
- Akeus, PaulinaGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xfaspa (author)
- Rodin, William,1994Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xrodwi (author)
- Raghavan, Sukanya,1974Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xragsu (author)
- Quiding-Järbrink, Marianne,1964Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xquima (author)
- Göteborgs universitetInstitutionen för biomedicin, avdelningen för mikrobiologi och immunologi (creator_code:org_t)
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