KONDO Tsunenori
   Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine
   Position   Professor
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 / ForeginForegin
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