BMC Cancer Research article FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy Hazem Ghebeh1, Eman Barhoush1, Asma Tulbah2, Naser Elkum3, Taher Al- Tweigeri4 and Said Dermime*1 BioMed Central Open Access Address: 1Tumor Immunology Section, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia, 2Department of Pathology, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia, 3Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia and 4King Faisal Cancer Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia Email: Hazem Ghebeh - hghebeh@kfshrc.edu.sa; Eman Barhoush - ebarhoush@kfshrc.edu.sa; Asma Tulbah - tulbah@kfshrc.edu.sa; Naser Elkum - nkum@kfshrc.edu.sa; Taher Al-Tweigeri - ttwegieri@kfshrc.edu.sa; Said Dermime* - sdermime@kfshrc.edu.sa * Corresponding author Published: 23 February 2008 BMC Cancer 2008, 8:57 doi:10.1186/1471-2407-8-57 This article is available from: http://www.biomedcentral.com/1471-2407/8/57 Received: 5 December 2007 Accepted: 23 February 2008 © 2008 Ghebeh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: 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 (Tregs). 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+ Tregs as a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated in vitro 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. Methods: 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. Results: A co-existence of B7-H1+ T lymphocytes and FOXP3+ Tregs was evidenced by the highly significant correlation of these molecules (P < .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3+ Tregs, B7-H1+ and PD-1+ TIL synergistically correlated with high histological grade (III) (P < .001), estrogen receptor negative status (P = .017), and the presence of severe lymphocytic infiltration (P = .022). Conclusion: 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 Tregs and B7-H1/PD-1 molecules. Page 1 of 12 (page number not for citation purposes)