Identification of targets for prostate cancer immunotherapy.
Prostate
; 79(5): 498-505, 2019 04.
Article
in En
| MEDLINE
| ID: mdl-30614027
ABSTRACT
BACKGROUND:
We performed profiling of the immune microenvironment of castration-resistant (CRPC) and castration-sensitive (CSPC) prostate cancer (PC) in order to identify novel targets for immunotherapy.METHODS:
PD-L1 and CD3/CD8 immunohistochemistry, PD-L1/2 fluorescent in situ hybridization, tumor mutation burden, microsatellite instability, and RNA-seq of 395 immune-related genes were performed in 19 CRPC and CSPC. Targeted genomic sequencing and fusion analysis were performed in 17 of these specimens.RESULTS:
CD276, PVR, and NECTIN2 were highly expressed in PC. Comparison of CRPC versus CSPC and primary versus metastatic tissue revealed the differential expression of immunostimulatory, immunosuppressive, and epithelial-to-mesenchymal transition (EMT)-related genes. Unsupervised clustering of differentially expressed genes yielded two final clusters best segregated by CRPC and CSPC status.CONCLUSION:
CD276 and the alternative checkpoint inhibition PVR/NECTIN2/CD226/TIGIT pathway emerged as relevant to PC checkpoint inhibition target development.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Prostatic Neoplasms, Castration-Resistant
Type of study:
Diagnostic_studies
Limits:
Aged
/
Humans
/
Male
/
Middle aged
Language:
En
Year:
2019
Type:
Article