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.
| Original language | English |
|---|---|
| Pages (from-to) | 1820-1828 |
| Number of pages | 9 |
| Journal | Cancer science |
| Volume | 110 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2019 Jun 1 |
Fingerprint
Keywords
- PD-1
- PD-L1
- renal cell carcinoma
- tumor microenvironment
- VEGF-TKI
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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.
In: Cancer science, Vol. 110, No. 6, 01.06.2019, p. 1820-1828.Research output: Contribution to journal › Article
}
TY - JOUR
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 - Tatsugami, Katsunori
AU - Takayama, Tatsuya
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.
KW - PD-1
KW - PD-L1
KW - renal cell carcinoma
KW - tumor microenvironment
KW - VEGF-TKI
UR - http://www.scopus.com/inward/record.url?scp=85066786724&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066786724&partnerID=8YFLogxK
U2 - 10.1111/cas.14019
DO - 10.1111/cas.14019
M3 - Article
C2 - 30972888
AN - SCOPUS:85066786724
VL - 110
SP - 1820
EP - 1828
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 6
ER -