Treg-cell depletion promotes chemokine production and accumulation of CXCR3(+) conventional T cells in intestinal tumors

European Journal of Immunology
Paulina AkeusMarianne Quiding-Järbrink

Abstract

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 ...Continue Reading

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Citations

Mar 20, 2016·International Immunopharmacology·Xin ChenZhiMing Huang
May 7, 2016·Advances in Medical Sciences·Mateusz RubinkiewiczAndrzej Budzyński
May 4, 2016·Oncoimmunology·Julie LeignadierImmanuel F Luescher
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Apr 11, 2017·European Journal of Immunology·Lydia Dyck, Kingston H G Mills
Nov 1, 2018·British Journal of Cancer·Shaheen KhanDavid E Gerber
Sep 22, 2019·International Journal of Molecular Sciences·Bilikis Aderonke AbolarinwaYen-Hua Huang
Apr 20, 2018·Cancer Immunology, Immunotherapy : CII·Paulina AkeusMarianne Quiding-Järbrink
Nov 28, 2018·World Journal of Gastroenterology : WJG·Sara Cabrero-de Las Heras, Eva Martínez-Balibrea
Mar 19, 2020·Cancer Immunology, Immunotherapy : CII·Louis SzeponikMarianne Quiding-Järbrink
Jul 18, 2020·Cancers·Jonadab E OlguínLuis I Terrazas
Feb 26, 2021·Frontiers in Oncology·Jun YangHushan Zhang
Jul 18, 2021·European Journal of Immunology·Paulina AkeusMarianne Quiding-Järbrink

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