FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy
<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T ce...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-02-01
|
| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/8/57 |
| _version_ | 1811277650506809344 |
|---|---|
| author | Al-Tweigeri Taher Elkum Naser Tulbah Asma Barhoush Eman Ghebeh Hazem Dermime Said |
| author_facet | Al-Tweigeri Taher Elkum Naser Tulbah Asma Barhoush Eman Ghebeh Hazem Dermime Said |
| author_sort | Al-Tweigeri Taher |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T<sub>regs</sub>). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T<sub>regs </sub>as a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated <it>in vitro </it>and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease.</p> <p>Methods</p> <p>Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease.</p> <p>Results</p> <p>A co-existence of B7-H1<sup>+ </sup>T lymphocytes and FOXP3<sup>+ </sup>T<sub>regs </sub>was evidenced by the highly significant correlation of these molecules (<it>P </it>< .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3<sup>+ </sup>T<sub>regs</sub>, B7-H1<sup>+ </sup>and PD-1<sup>+ </sup>TIL synergistically correlated with high histological grade (III) (<it>P </it>< .001), estrogen receptor negative status (<it>P </it>= .017), and the presence of severe lymphocytic infiltration (<it>P </it>= .022).</p> <p>Conclusion</p> <p>Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T<sub>regs </sub>and B7-H1/PD-1 molecules.</p> |
| first_indexed | 2024-04-13T00:19:32Z |
| format | Article |
| id | doaj.art-d7a3bfa9afca4bce98719ee1382ba48f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T00:19:32Z |
| publishDate | 2008-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d7a3bfa9afca4bce98719ee1382ba48f2022-12-22T03:10:49ZengBMCBMC Cancer1471-24072008-02-01815710.1186/1471-2407-8-57FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapyAl-Tweigeri TaherElkum NaserTulbah AsmaBarhoush EmanGhebeh HazemDermime Said<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T<sub>regs</sub>). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T<sub>regs </sub>as a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated <it>in vitro </it>and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease.</p> <p>Methods</p> <p>Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease.</p> <p>Results</p> <p>A co-existence of B7-H1<sup>+ </sup>T lymphocytes and FOXP3<sup>+ </sup>T<sub>regs </sub>was evidenced by the highly significant correlation of these molecules (<it>P </it>< .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3<sup>+ </sup>T<sub>regs</sub>, B7-H1<sup>+ </sup>and PD-1<sup>+ </sup>TIL synergistically correlated with high histological grade (III) (<it>P </it>< .001), estrogen receptor negative status (<it>P </it>= .017), and the presence of severe lymphocytic infiltration (<it>P </it>= .022).</p> <p>Conclusion</p> <p>Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T<sub>regs </sub>and B7-H1/PD-1 molecules.</p>http://www.biomedcentral.com/1471-2407/8/57 |
| spellingShingle | Al-Tweigeri Taher Elkum Naser Tulbah Asma Barhoush Eman Ghebeh Hazem Dermime Said FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy BMC Cancer |
| title | FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy |
| title_full | FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy |
| title_fullStr | FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy |
| title_full_unstemmed | FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy |
| title_short | FOXP3<sup>+ </sup>T<sub>regs </sub>and B7-H1<sup>+</sup>/PD-1<sup>+ </sup>T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy |
| title_sort | foxp3 sup sup t sub regs sub and b7 h1 sup sup pd 1 sup sup t lymphocytes co infiltrate the tumor tissues of high risk breast cancer patients implication for immunotherapy |
| url | http://www.biomedcentral.com/1471-2407/8/57 |
| work_keys_str_mv | AT altweigeritaher foxp3supsuptsubregssubandb7h1supsuppd1supsuptlymphocytescoinfiltratethetumortissuesofhighriskbreastcancerpatientsimplicationforimmunotherapy AT elkumnaser foxp3supsuptsubregssubandb7h1supsuppd1supsuptlymphocytescoinfiltratethetumortissuesofhighriskbreastcancerpatientsimplicationforimmunotherapy AT tulbahasma foxp3supsuptsubregssubandb7h1supsuppd1supsuptlymphocytescoinfiltratethetumortissuesofhighriskbreastcancerpatientsimplicationforimmunotherapy AT barhousheman foxp3supsuptsubregssubandb7h1supsuppd1supsuptlymphocytescoinfiltratethetumortissuesofhighriskbreastcancerpatientsimplicationforimmunotherapy AT ghebehhazem foxp3supsuptsubregssubandb7h1supsuppd1supsuptlymphocytescoinfiltratethetumortissuesofhighriskbreastcancerpatientsimplicationforimmunotherapy AT dermimesaid foxp3supsuptsubregssubandb7h1supsuppd1supsuptlymphocytescoinfiltratethetumortissuesofhighriskbreastcancerpatientsimplicationforimmunotherapy |