Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer.

Détails

ID Serval
serval:BIB_F22DB3702D29
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer.
Périodique
Cancer Research
Auteur(s)
Woo E.Y., Chu C.S., Goletz T.J., Schlienger K., Yeh H., Coukos G., Rubin S.C., Kaiser L.R., June C.H.
ISSN
0008-5472 (Print)
ISSN-L
0008-5472
Statut éditorial
Publié
Date de publication
2001
Volume
61
Numéro
12
Pages
4766-4772
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Immunosuppression may contribute to the progression of cancer. In this study we assessed the structural and functional status of T cells from tumor specimens obtained from patients with early stage non-small cell lung cancer and late-stage ovarian cancer. Although some groups have described structural alterations in the TCR in patients with other malignancies, we did not observe decreased expression of the CD3zeta subunit in the tumor-associated T cells. However, increased percentages of CD4(+)CD25(+) T cells were observed in the non-small cell lung cancer tumor-infiltrating lymphocytes and ovarian cancer tumor-associated lymphocytes. Furthermore, these CD4(+)CD25(+) T cells were found to secrete transforming growth factor-beta, consistent with the phenotype of regulatory T cells. Despite a generalized expression of lymphocyte activation markers in the tumor-associated T-cell populations, the CD8(+) T cells expressed low levels of CD25. To determine whether expression of CD25 could be restored on the CD8 cells, tumor-associated T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. After stimulation, nearly all of the CD8 T cells expressed CD25. Furthermore, despite the low levels of interleukin 2, IFN-gamma, and tumor necrosis factor-alpha secretion by the tumor-associated and peripheral blood T cells at baseline, stimulation with anti-CD3 and anti-CD28 monoclonal antibodies significantly increased the fraction of cells producing these cytokines. Thus, tumor-associated T cells from patients with early and late-stage epithelial tumors contain increased proportions of CD4(+)CD25(+) T cells that secrete the immunosuppressive cytokine transforming growth factor-beta. Furthermore, our results are consistent with previous reports showing impaired expression of CD25 on CD8(+) T cells in cancer patients. Finally, increased lymphocyte costimulation provided by triggering the CD28 receptor is able to increase CD25 expression and cytokine secretion in tumor-associated T cells. These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients.
Mots-clé
Antigens, CD3/biosynthesis, Antigens, CD4/biosynthesis, Antigens, CD4/immunology, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/metabolism, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Carcinoma, Non-Small-Cell Lung/immunology, Carcinoma, Non-Small-Cell Lung/metabolism, Down-Regulation, Female, Humans, Interferon-gamma/biosynthesis, Interleukin-2/biosynthesis, Lung Neoplasms/immunology, Lung Neoplasms/metabolism, Lymphocyte Activation/immunology, Lymphocytes, Tumor-Infiltrating/immunology, Neoplasm Staging, Ovarian Neoplasms/immunology, Ovarian Neoplasms/metabolism, Receptors, Antigen, T-Cell/biosynthesis, Receptors, Interleukin-2/biosynthesis, Receptors, Interleukin-2/immunology, Th1 Cells/immunology, Th1 Cells/metabolism, Transforming Growth Factor beta/secretion, Tumor Necrosis Factor-alpha/biosynthesis
Pubmed
Création de la notice
14/10/2014 12:43
Dernière modification de la notice
03/03/2018 22:39
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