Tumor-Expressed B7-H1 and B7-DC in Relation to PD-1+ T-Cell Infiltration and Survival of Patients with Cervical Carcinoma

• Published in: Clinical cancer research 2009-10, Vol.15 (20), p.6341-6347
• Main Authors: Karim, Rezaul, Jordanova, Ekaterina S, Piersma, Sytse J, Kenter, Gemma G, Chen, Lieping, Boer, Judith M, Melief, Cornelis J M, van der Burg, Sjoerd H
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Antineoplastic agents; Apoptosis Regulatory Proteins - metabolism; B7-1 Antigen - metabolism; B7-H1 Antigen; Biological and medical sciences; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating - metabolism; Medical sciences; Pharmacology. Drug treatments; Programmed Cell Death 1 Ligand 2 Protein; Programmed Cell Death 1 Receptor; T-Lymphocyte Subsets; T-Lymphocytes; T-Lymphocytes, Regulatory - metabolism; Tumors; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - mortality
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-1652

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. (Clin Cancer Res 2009;15(20):6341–7)