The role of PD-L1 in the radiation response and clinical outcome for bladder cancer

被引:163
作者
Wu, Chun-Te [1 ,2 ]
Chen, Wen-Cheng [2 ,3 ]
Chang, Ying-Hsu [4 ]
Lin, Wei-Yu [2 ,5 ]
Chen, Miao-Fen [2 ,3 ]
机构
[1] Chang Gung Mem Hosp, Dept Urol, Keelung, Taiwan
[2] Chang Gung Univ, Coll Med, Taoyuan, Taiwan
[3] Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan
[4] Chang Gung Mem Hosp, Dept Urol, Linkou, Taiwan
[5] Chang Gung Mem Hosp, Urol, Chiayi, Taiwan
关键词
RADICAL CYSTECTOMY; ANTITUMOR IMMUNITY; TUMOR-CELLS; IMMUNOTHERAPY; RADIOTHERAPY; EXPRESSION; CARCINOMA; B7-H1; IRRADIATION; PROGRESSION;
D O I
10.1038/srep19740
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Identification of potential factors that can stratify a tumor's response to specific therapies will aid in the selection of cancer therapy. The aim was to highlight the role of programmed cell death 1 ligand 1 (PD-L1) in bladder cancer. In this study, 92 of muscle-invasive bladder cancers and 28 of non-muscle invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human and murine bladder cancer cell lines were used to examine the correlation between PD-L1 and radiation response. Our data revealed that PD-L1 was overexpressed in the bladder tumor specimens compared with adjacent non-malignant specimens. Furthermore, the staining of PD-L1 was significantly linked to higher clinical stage, lower complete response rates and reduced disease-free survival rates. By in vitro and in vivo experiments, irradiation up-regulated the expression of PD-L1 in tumor cells, and its increase correlated with the irradiation dose. In immunocompetent mouse models, blocking PD-L1 induced a longer tumour growth delay following irradiation. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells was responsible to the effects of PD-L1 on radiation response. In conclusion, PD-L1 could be a significant clinical predictor for clinical stage and treatment response of bladder cancer.
引用
收藏
页数:9
相关论文
共 35 条
[1]  
Afreen Sehar, 2014, Hematol Oncol Stem Cell Ther, V7, P1, DOI 10.1016/j.hemonc.2013.09.005
[2]   Molecular Pathways: Next-Generation Immunotherapy-Inhibiting Programmed Death-Ligand 1 and Programmed Death-1 [J].
Chen, Daniel S. ;
Irving, Bryan A. ;
Hodi, F. Stephen .
CLINICAL CANCER RESEARCH, 2012, 18 (24) :6580-6587
[3]   1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling [J].
Chen, Ping-Tsung ;
Hsieh, Ching-Chuan ;
Wu, Chun-Te ;
Yen, Tzu-Chen ;
Lin, Paul-Yang ;
Chen, Wen-Cheng ;
Chen, Miao-Fen .
MOLECULAR CANCER THERAPEUTICS, 2015, 14 (06) :1365-1375
[4]   Radiation and anti-PD-L1 antibody combinatorial therapy induces T cell-mediated depletion of myeloid-derived suppressor cells and tumor regression [J].
Deng, Liufu ;
Liang, Hua ;
Burnette, Byron ;
Weichselbaum, Ralph R. ;
Fu, Yang-Xin .
ONCOIMMUNOLOGY, 2014, 3 (04)
[5]   Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice [J].
Deng, Liufu ;
Liang, Hua ;
Burnette, Byron ;
Beckett, Michael ;
Darga, Thomas ;
Weichselbaum, Ralph R. ;
Fu, Yang-Xin .
JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (02) :687-695
[6]   Focus on bladder cancer [J].
Dinney, CPN ;
McConkey, DJ ;
Millikan, RE ;
Wu, XF ;
Bar-Eli, M ;
Adam, L ;
Kamat, AM ;
Siefker-Radtke, AO ;
Tuziak, T ;
Sabichi, AL ;
Grossman, HB ;
Benedict, WF ;
Czerniak, B .
CANCER CELL, 2004, 6 (02) :111-116
[7]  
Dong HD, 2002, NAT MED, V8, P793, DOI 10.1038/nm730
[8]   Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade [J].
Dovedi, Simon J. ;
Adlard, Amy L. ;
Lipowska-Bhalla, Grazyna ;
McKenna, Conor ;
Jones, Sherrie ;
Cheadle, Eleanor J. ;
Stratford, Ian J. ;
Poon, Edmund ;
Morrow, Michelle ;
Stewart, Ross ;
Jones, Hazel ;
Wilkinson, Robert W. ;
Honeychurch, Jamie ;
Illidge, Tim M. .
CANCER RESEARCH, 2014, 74 (19) :5458-5468
[9]   Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift [J].
Formenti, Silvia C. ;
Demaria, Sandra .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2013, 105 (04) :256-265
[10]   The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: Correlation with important high-risk prognostic factors [J].
Ghebeh, Hazem ;
Mohammed, Shamayel ;
Al-Omair, Abeer ;
Qattan, Amal ;
Lehe, Cynthia ;
Al-Qudaihi, Ghofran ;
Elkum, Naser ;
Alshabanah, Mohamed ;
Bin Amer, Suad ;
Tulbah, Asma ;
Ajarim, Dahish ;
Al-Tweigeri, Taher ;
Dermime, Said .
NEOPLASIA, 2006, 8 (03) :190-198