Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma.

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.

• Authors: Rezaul Karim, Ekaterina S Jordanova, Sytse J Piersma, Gemma G Kenter, Lieping Chen, Judith M Boer, Cornelis J M Melief, Sjoerd H van der Burg
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 20 Pg. 6341-7 (Oct 15 2009) ISSN: 1557-3265 [Electronic] United States
• PMID: 19825956 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Apoptosis Regulatory Proteins
• B7-1 Antigen
• B7-H1 Antigen
• CD274 protein, human
• PDCD1 protein, human
• PDCD1LG2 protein, human
• Programmed Cell Death 1 Ligand 2 Protein
• Programmed Cell Death 1 Receptor

Topics

• Antigens, CD (metabolism)
• Apoptosis Regulatory Proteins (metabolism)
• B7-1 Antigen (metabolism)
• B7-H1 Antigen
• Female
• Humans
• Lymphocyte Activation
• Lymphocytes, Tumor-Infiltrating (metabolism)
• Programmed Cell Death 1 Ligand 2 Protein
• Programmed Cell Death 1 Receptor
• T-Lymphocyte Subsets
• T-Lymphocytes
• T-Lymphocytes, Regulatory (metabolism)
• Uterine Cervical Neoplasms (metabolism, mortality)