KONDO Tsunenori
Department School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine Position Professor |
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Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma. |
Journal | Formal name:Cancer science Abbreviation:Cancer Sci ISSN code:13497006/13479032 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 110(6),pp.1820-1828 |
Author and coauthor | Mikami Shuji, Mizuno Ryuichi, Kondo Tsunenori, Shinohara Nobuo, Nonomura Norio, Ozono Seiichiro, Eto Masatoshi, Tatsugami Katsunori, Takayama Tatsuya, Matsuyama Hideyasu, Kishida Takeshi, Oya Mototsugu, |
Publication date | 2019/06 |
Summary | 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 |