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The Ratios of CD8(+) T Cells to CD4(+)CD25(+) FOXP3(+) and FOXP3(-) T Cells Correlate with Poor Clinical Outcome in Human Serous Ovarian Cancer

Ovarian cancer is an immune reactive malignancy with a complex immune suppressive network that blunts successful immune eradication. This suppressive microenvironment may be mediated by recruitment or induction of CD4(+) regulatory T cells (Tregs). Our study sought to investigate the association of...

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Detalles Bibliográficos
Autores principales: Preston, Claudia C., Maurer, Matthew J., Oberg, Ann L., Visscher, Daniel W., Kalli, Kimberly R., Hartmann, Lynn C., Goode, Ellen L., Knutson, Keith L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828213/
https://www.ncbi.nlm.nih.gov/pubmed/24244610
http://dx.doi.org/10.1371/journal.pone.0080063
Descripción
Sumario:Ovarian cancer is an immune reactive malignancy with a complex immune suppressive network that blunts successful immune eradication. This suppressive microenvironment may be mediated by recruitment or induction of CD4(+) regulatory T cells (Tregs). Our study sought to investigate the association of tumor-infiltrating CD4(+)CD25(+)FOXP3(+) Tregs, and other immune factors, with clinical outcome in serous ovarian cancer patients. We performed immunofluorescence and quantification of intraepithelial tumor-infiltrating triple positive Tregs (CD4(+)CD25(+)FOXP3(+)), as well as CD4(+)CD25(+)FOXP3(-), CD3(+) and CD8(+) T cells in tumor specimens from 52 patients with high stage serous ovarian carcinoma. Thirty-one of the patients had good survival (i.e. > 60 months) and 21 had poor survival of < 18 months. Total cell counts as well as cell ratios were compared among these two outcome groups. The total numbers of CD4(+)CD25(+)FOXP3(+) Tregs, CD4(+)CD25(+)FOXP3(-), CD3(+) and CD8(+) cells were not significantly different between the groups. However, higher ratios of CD8(+)/CD4(+)CD25(+)FOXP3(+) Treg, CD8(+)/CD4(+) and CD8/CD4(+)CD25(+)FOXP3(-) cells were seen in the good outcome group when compared to the patients with poor outcome. These data show for the first time that the ratios of CD8(+) to both CD4(+)CD25(+)FOXP3(+) Tregs and CD4(+)CD25(+)FOXP3(-) T cells are associated with disease outcome in ovarian cancer. The association being apparent in ratios rather than absolute count of T cells suggests that the effector/suppressor ratio may be a more important indicator of outcome than individual cell count. Thus, immunotherapy strategies that modify the ratio of CD4(+)CD25(+)FOXP3(+) Tregs or CD4(+)CD25(+)FOXP3(-) T cells to CD8(+) effector cells may be useful in improving outcomes in ovarian cancer.