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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3828213?pdf=render |
| _version_ | 1830343248170713088 |
|---|---|
| author | Claudia C Preston Matthew J Maurer Ann L Oberg Daniel W Visscher Kimberly R Kalli Lynn C Hartmann Ellen L Goode Keith L Knutson |
| author_facet | Claudia C Preston Matthew J Maurer Ann L Oberg Daniel W Visscher Kimberly R Kalli Lynn C Hartmann Ellen L Goode Keith L Knutson |
| author_sort | Claudia C Preston |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T22:05:59Z |
| format | Article |
| id | doaj.art-8d9878a5d7b840609d541c662507c135 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T22:05:59Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8d9878a5d7b840609d541c662507c1352022-12-21T20:04:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8006310.1371/journal.pone.0080063The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer.Claudia C PrestonMatthew J MaurerAnn L ObergDaniel W VisscherKimberly R KalliLynn C HartmannEllen L GoodeKeith L KnutsonOvarian 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.http://europepmc.org/articles/PMC3828213?pdf=render |
| spellingShingle | Claudia C Preston Matthew J Maurer Ann L Oberg Daniel W Visscher Kimberly R Kalli Lynn C Hartmann Ellen L Goode Keith L Knutson The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer. PLoS ONE |
| title | The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer. |
| title_full | The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer. |
| title_fullStr | The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer. |
| title_full_unstemmed | The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer. |
| title_short | The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer. |
| title_sort | ratios of cd8 t cells to cd4 cd25 foxp3 and foxp3 t cells correlate with poor clinical outcome in human serous ovarian cancer |
| url | http://europepmc.org/articles/PMC3828213?pdf=render |
| work_keys_str_mv | AT claudiacpreston theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT matthewjmaurer theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT annloberg theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT danielwvisscher theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT kimberlyrkalli theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT lynnchartmann theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT ellenlgoode theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT keithlknutson theratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT claudiacpreston ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT matthewjmaurer ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT annloberg ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT danielwvisscher ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT kimberlyrkalli ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT lynnchartmann ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT ellenlgoode ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer AT keithlknutson ratiosofcd8tcellstocd4cd25foxp3andfoxp3tcellscorrelatewithpoorclinicaloutcomeinhumanserousovariancancer |