コンドウ　ツネノリ   KONDO Tsunenori   近藤　恒徳    所属   医学部 医学科（附属足立医療センター）    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma.
掲載誌名	正式名：Cancer science 略　 称：Cancer Sci ISSNコード：13497006/13479032
掲載区分	国外
巻・号・頁	110(6),pp.1820-1828
著者・共著者	Mikami Shuji, Mizuno Ryuichi, Kondo Tsunenori, Shinohara Nobuo, Nonomura Norio, Ozono Seiichiro, Eto Masatoshi, Tatsugami Katsunori, Takayama Tatsuya, Matsuyama Hideyasu, Kishida Takeshi, Oya Mototsugu,
発行年月	2019/06
概要	Recently, immunotherapy based on blocking immune checkpoints with programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) Abs has been introduced for the treatment of advanced clear cell renal cell carcinoma (ccRCC), especially tumors resistant to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs), but the significance of their expression in the tumor microenvironment is unclear. We investigated these immune checkpoint markers in tumor cells and tumor-infiltrating immune cells (TIIC) in the tumor microenvironment of 100 untreated and 25 VEGF-TKI-treated primary ccRCC tissues. Upregulated expression of PD-1 and PD-L1 by TIIC, and PD-L1 by tumor cells was associated with the histological grade and unfavorable prognosis of RCC patients. High PD-1 and PD-L1 expression by TIIC was associated with a poorer response to VEGF-TKI, whereas PD-L1 expression by tumor cells did not affect the efficacy of the treatment. Furthermore, increased PD-1-positive TIIC and PD-L1-positive TIIC were observed in tumors treated with VEGF-TKIs compared with those in untreated tumors. Our data suggest that PD-1 and PD-L1 expression by TIIC in the tumor microenvironment is involved in treatment resistance, and that sequential therapy with immune checkpoint inhibitors could be a promising therapeutic strategy for ccRCC resistant to VEGF-TKI treatment.
DOI	10.1111/cas.14019
PMID	30972888