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  • Title: Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma.
    Author: Karim R, Jordanova ES, Piersma SJ, Kenter GG, Chen L, Boer JM, Melief CJ, van der Burg SH.
    Journal: Clin Cancer Res; 2009 Oct 15; 15(20):6341-7. PubMed ID: 19825956.
    Abstract:
    PURPOSE: The interaction between programmed cell death 1 (PD-1), expressed by activated effector or regulatory T cells, and B7-H1 (PD-L1) and B7-DC (PD-L2) results in the inhibition of T-cell function. The aim of this study was to determine B7-H1, B7-DC, and PD-1 expression in cervical carcinoma. EXPERIMENTAL DESIGN: A tissue microarray of a well-defined group of 115 patients was stained with antibodies against B7-H1 and B7-DC. Three-color fluorescent immunohistochemistry was used to study the number and phenotype of tumor-infiltrating T cells expressing PD-1. Additional analyses consisted of in vitro T-cell suppression assays. RESULTS: B7-H1 was expressed in 19%, and B7-DC was expressed by 29% of the 115 tumors. PD-1 was expressed by more than half of both the infiltrating CD8+ T cells and CD4+Foxp3+ T cells, irrespective of B7-H1 or B7-DC expression by tumors. The expression of B7-H1 did not show a direct impact on patient survival. However, subgroup analysis revealed that patients with a relative excess of infiltrating regulatory T cells displayed a better survival when the tumor was B7-H1 positive (P = 0.033). Additional studies showed that the presence of B7-H1 during the activation of CD4+Foxp3+ regulatory T cells impaired their suppressive function in a functional in vitro assay. CONCLUSIONS: B7-H1 is expressed on only a minority of cervical cancers and does not influence the survival of patients with cervical cancer. PD-1 is expressed by a vast number of infiltrating CD8 T cells, suggesting that blocking of PD-1 could have therapeutic potential in cervical cancer patients.
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