PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab. (2nd December 2018)

• Record Type: Journal Article
• Authors: George, Saby; Papanicolau-Sengos, Antonios; Lenzo, Felicia L.; Conroy, Jeffrey M.; Nesline, Mary; Pabla, Sarabjot; Glenn, Sean T.; Burgher, Blake; Andreas, Jonathan; Giamo, Vincent; Qin, Moachun; Wang, Yirong; Galluzzi, Lorenzo; Morrison, Carl
• Is Part Of: Oncoimmunology. Volume 7:Number 12(2018)
• Publication Date: 2018-12-02
• Subjects: 22C3 assay -- ADORA2A -- atezolizumab -- immunohistochemistry -- PD-1 -- SP142 assay; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1460298
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: We report the immunological profile of a patient with upper-tract urothelial carcinoma experiencing stable disease on pembrolizumab for 20 months. The tumor exhibited extensive infiltration by CD8 + cytotoxic T lymphocytes, low-to-moderate mutational burden, no PD-L1 staining by commercially available immunohistochemical assays, but amplification of CD274 (coding for PD-L1) and/or PDCD1LG2 (encoding PD-L2) by fluorescence in situ hybridization. RNA-seq revealed multiple biomarkers of an ongoing immune response and compensatory immune evasion, including moderate PD-L1 levels coupled with robust PD-L2 expression. Pending validation in additional patients, these findings suggest that PD-L2 expression levels may constitute a biomarker of response to immune checkpoint blockade in urothelial carcinoma.