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Clinical Cancer Research Vol. 10, 5094-5100, August 1, 2004
© 2004 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

B7-H1 Expression on Non-Small Cell Lung Cancer Cells and Its Relationship with Tumor-Infiltrating Lymphocytes and Their PD-1 Expression

Jun Konishi1, Koichi Yamazaki1, Miyuki Azuma2, Ichiro Kinoshita3, Hirotoshi Dosaka-Akita3 and Masaharu Nishimura1

1 First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan; 2 Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan; and 3 Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Purpose: B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs.

Experimental Design: The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically.

Results: Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02).

Conclusions: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2004 by the American Association for Cancer Research.