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Human epithelial ovarian carcinoma cell-derived cytokines cooperatively induce activated CD4+CD25-CD45RA+ naïve T cells to express forkhead box protein 3 and exhibit suppressive ability in vitro.
Cancer Sci. 2009 Nov; 100(11):2143-51.CS

Abstract

Regulatory T cells play an important role in tumor escape from host antitumor immunity. Increased frequencies of CD4(+)CD25(+) regulatory T cells have been documented in the tumor sites, malignant effusions, and peripheral blood of patients with ovarian carcinoma. However, the mechanism involved remains unclear. In the present study, we collected high-purity human CD4(+)CD25(-)CD45RA(+) naïve T cells by microbead cell separation. These cells did not express FOXP3 by single-cell analysis, and few cells expressed FOXP3 when they were activated with anti-CD3/CD28 dual signal. However, more cells expressed FOXP3 when the supernatant of human epithelial ovarian carcinoma cell culture was added, yet not the supernatant of normal human ovarian surface epithelia cell culture. Neutralization assays revealed that neutralizing antibody against transforming growth factor beta (TGF-beta), interleukin-10, and interleukin-4 did not abrogate elevated FOXP3 expression induced by carcinoma cell culture supernatant, whereas neutralizing leukemia inhibitory factor (LIF) partially abrogated FOXP3 expression, but LIF alone could not increase FOXP3 expression in activated naïve T cells. Further, an in vitro coculture suppression assay showed that these cells could suppress the proliferation of autologous CD4(+)CD25(-)CD45RA(-) T cells. In summary, our findings show that ovarian carcinoma cells are able to induce expression of FOXP3 and exhibit suppressive ability in activated naïve T cells by producing soluble substances, and multiple cytokines involve in the induction of FOXP3 expression.

Authors+Show Affiliations

Department of Gynecology and Obstetrics, Sir Run Run Shaw Hospital, Hangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19673890

Citation

Zhao, Xiaofeng, et al. "Human Epithelial Ovarian Carcinoma Cell-derived Cytokines Cooperatively Induce Activated CD4+CD25-CD45RA+ Naïve T Cells to Express Forkhead Box Protein 3 and Exhibit Suppressive Ability in Vitro." Cancer Science, vol. 100, no. 11, 2009, pp. 2143-51.
Zhao X, Ye F, Chen L, et al. Human epithelial ovarian carcinoma cell-derived cytokines cooperatively induce activated CD4+CD25-CD45RA+ naïve T cells to express forkhead box protein 3 and exhibit suppressive ability in vitro. Cancer Sci. 2009;100(11):2143-51.
Zhao, X., Ye, F., Chen, L., Lu, W., & Xie, X. (2009). Human epithelial ovarian carcinoma cell-derived cytokines cooperatively induce activated CD4+CD25-CD45RA+ naïve T cells to express forkhead box protein 3 and exhibit suppressive ability in vitro. Cancer Science, 100(11), 2143-51. https://doi.org/10.1111/j.1349-7006.2009.01286.x
Zhao X, et al. Human Epithelial Ovarian Carcinoma Cell-derived Cytokines Cooperatively Induce Activated CD4+CD25-CD45RA+ Naïve T Cells to Express Forkhead Box Protein 3 and Exhibit Suppressive Ability in Vitro. Cancer Sci. 2009;100(11):2143-51. PubMed PMID: 19673890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human epithelial ovarian carcinoma cell-derived cytokines cooperatively induce activated CD4+CD25-CD45RA+ naïve T cells to express forkhead box protein 3 and exhibit suppressive ability in vitro. AU - Zhao,Xiaofeng, AU - Ye,Feng, AU - Chen,Lili, AU - Lu,Weiguo, AU - Xie,Xing, Y1 - 2009/07/10/ PY - 2009/8/14/entrez PY - 2009/8/14/pubmed PY - 2009/11/5/medline SP - 2143 EP - 51 JF - Cancer science JO - Cancer Sci VL - 100 IS - 11 N2 - Regulatory T cells play an important role in tumor escape from host antitumor immunity. Increased frequencies of CD4(+)CD25(+) regulatory T cells have been documented in the tumor sites, malignant effusions, and peripheral blood of patients with ovarian carcinoma. However, the mechanism involved remains unclear. In the present study, we collected high-purity human CD4(+)CD25(-)CD45RA(+) naïve T cells by microbead cell separation. These cells did not express FOXP3 by single-cell analysis, and few cells expressed FOXP3 when they were activated with anti-CD3/CD28 dual signal. However, more cells expressed FOXP3 when the supernatant of human epithelial ovarian carcinoma cell culture was added, yet not the supernatant of normal human ovarian surface epithelia cell culture. Neutralization assays revealed that neutralizing antibody against transforming growth factor beta (TGF-beta), interleukin-10, and interleukin-4 did not abrogate elevated FOXP3 expression induced by carcinoma cell culture supernatant, whereas neutralizing leukemia inhibitory factor (LIF) partially abrogated FOXP3 expression, but LIF alone could not increase FOXP3 expression in activated naïve T cells. Further, an in vitro coculture suppression assay showed that these cells could suppress the proliferation of autologous CD4(+)CD25(-)CD45RA(-) T cells. In summary, our findings show that ovarian carcinoma cells are able to induce expression of FOXP3 and exhibit suppressive ability in activated naïve T cells by producing soluble substances, and multiple cytokines involve in the induction of FOXP3 expression. SN - 1349-7006 UR - https://www.unboundmedicine.com/medline/citation/19673890/Human_epithelial_ovarian_carcinoma_cell_derived_cytokines_cooperatively_induce_activated_CD4+CD25_CD45RA+_naïve_T_cells_to_express_forkhead_box_protein_3_and_exhibit_suppressive_ability_in_vitro_ L2 - https://doi.org/10.1111/j.1349-7006.2009.01286.x DB - PRIME DP - Unbound Medicine ER -