Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma

the Japanese Society of Renal Cancer

研究成果: ジャーナルへの寄稿記事

抄録

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.

元の言語英語
ページ(範囲)1820-1828
ページ数9
ジャーナルCancer Science
110
発行部数6
DOI
出版物ステータス出版済み - 6 1 2019

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Tumor Microenvironment
Renal Cell Carcinoma
Ligands
Neoplasms
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Therapeutics
Immunotherapy
Biomarkers

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma. / the Japanese Society of Renal Cancer.

:: Cancer Science, 巻 110, 番号 6, 01.06.2019, p. 1820-1828.

研究成果: ジャーナルへの寄稿記事

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title = "Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma",
abstract = "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.",
author = "{the Japanese Society of Renal Cancer} and Shuji Mikami and Ryuichi Mizuno and Tsunenori Kondo and Nobuo Shinohara and Norio Nonomura and Seiichiro Ozono and Masatoshi Eto and Masatoshi Eto and Katsunori Tatsugami and Hideyasu Matsuyama and Takeshi Kishida and Mototsugu Oya",
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T1 - Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma

AU - the Japanese Society of Renal Cancer

AU - Mikami, Shuji

AU - Mizuno, Ryuichi

AU - Kondo, Tsunenori

AU - Shinohara, Nobuo

AU - Nonomura, Norio

AU - Ozono, Seiichiro

AU - Eto, Masatoshi

AU - Eto, Masatoshi

AU - Tatsugami, Katsunori

AU - Matsuyama, Hideyasu

AU - Kishida, Takeshi

AU - Oya, Mototsugu

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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