Dataset Information

Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer.

ABSTRACT: Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39⁺ γδTreg in human colorectal cancer (CRC). CD39⁺ γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4⁺ or CD8⁺ Tregs via the adenosine-mediated pathway but independent of TGF-β or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network. We further demonstrate that tumor-derived TGF-β1 induces CD39⁺ γδT cells from paired normal colon tissues to produce more adenosine and become potent immunosuppressive T cells. Moreover, CD39⁺ γδTreg infiltration is positively correlated with TNM stage and other unfavorable clinicopathological features, implicating that CD39⁺ γδTregs are one of the key players in establishment of immunosuppressive TME in human CRC that may be critical for tumor immunotherapy.

SUBMITTER: Hu G

PROVIDER: S-EPMC5353931 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Tumor-infiltrating CD39+γδTregs are novel immunosuppressive T cells in human colorectal cancer.

Hu Guoming G Wu Pin P Cheng Pu P Zhang Zhigang Z Wang Zhen Z Yu Xiuyan X Shao Xuan X Wu Dang D Ye Jun J Zhang Tao T Wang Xiaochen X Qiu Fuming F Yan Jun J Huang Jian J

Oncoimmunology 20170106 2

Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39+ γδTreg in human colorectal cancer (CRC). CD39+ γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4+ or CD8+ Tregs via the adenosine-mediated pathway but independent of TGF-β or IL ...[more]

PMID: 28344891

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Project description:BackgroundCongenital cytomegalovirus (cCMV) infection can lead to a range of adverse outcomes. The majority of cCMV neonates with clinical symptoms are infected postnatally; however, established cases of intrauterine infection are uncommon, resulting in a paucity of reports on clinical findings and lymphocytes expression in CMV-infected neonates.Case presentationWe followed a neonate with cCMV infection from the onset of hospitalization to several months of follow-up. This infant was intrauterine CMV-positive in the amniotic fluid of the mother at 21 weeks' gestation and received intravenous ganciclovir infusion and sequential oral valganciclovir after birth. The typical clinical signs manifested in the nervous system, liver, and peripheral blood and were documented during the hospitalizaion period and up to the follow-up visit. Flow cytometry was employed to examine the expression of T cells, their subsets, and the associated cytokines in peripheral blood samples at various time points. The flow data for the cCMV neonate were compared with those of the controls at each time point. Following treatment, clinical symptoms improved and the infant became CMV negative. However, developmental delays occurred later in life. The proportion of CD8+CD28- Tregs in the peripheral blood of the neonate with congenital CMV infection was higher than that in the controls at the three time points. The expression levels of perforin and granzyme B secreted by γδ T cells (Vδ1 and Vδ2 T cells), increased during the course of hospitalization until follow-up and were higher than those in the controls at the three time points.ConclusionsDespite the alleviation of clinical symptoms, developmental delay in later life remains inevitable in this intrauterine cCMV neonate. CD8+CD28- Tregs and Vδ1 and Vδ2 T cells secreting perforin and granzyme B may be involved in congenital CMV infection, although this hypothesis requires validation in a larger study. This report may contribute to our understanding of the effect of current treatment and the immune status of intrauterine cCMV-infected neonates.

Dataset Information

Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer.

Publications

Tumor-infiltrating CD39<sup>+</sup><b>γ</b><b>δ</b>Tregs are novel immunosuppressive T cells in human colorectal cancer.

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