PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

Saby George; Antonios Papanicolau-Sengos; Felicia L. Lenzo; Jeffrey M. Conroy; Mary Nesline; Sarabjot Pabla; Sean T. Glenn; Blake Burgher; Jonathan Andreas; Vincent Giamo; Moachun Qin; Yirong Wang; Lorenzo Galluzzi; Carl Morrison

doi:10.1080/2162402X.2018.1460298

PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

Saby George, Antonios Papanicolau-Sengos, Felicia L. Lenzo, Jeffrey M. Conroy, Mary Nesline, Sarabjot Pabla, Sean T. Glenn, Blake Burgher, Jonathan Andreas, Vincent Giamo, Moachun Qin, Yirong Wang, Lorenzo Galluzzi, Carl Morrison

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Article number	e1460298
Journal	Oncoimmunology
Volume	7
Issue number	12
DOIs	https://doi.org/10.1080/2162402X.2018.1460298
State	Published - Dec 2 2018
Externally published	Yes

Keywords

22C3 assay
ADORA2A
atezolizumab
immunohistochemistry
PD-1
SP142 assay

Access to Document

10.1080/2162402X.2018.1460298

Cite this

George, S., Papanicolau-Sengos, A., Lenzo, F. L., Conroy, J. M., Nesline, M., Pabla, S., Glenn, S. T., Burgher, B., Andreas, J., Giamo, V., Qin, M., Wang, Y., Galluzzi, L., & Morrison, C. (2018). PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab. Oncoimmunology, 7(12), Article e1460298. https://doi.org/10.1080/2162402X.2018.1460298

@article{87fa2ac69787440c97c87768777ebe92,

title = "PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab",

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.",

keywords = "22C3 assay, ADORA2A, atezolizumab, immunohistochemistry, PD-1, SP142 assay",

author = "Saby George and Antonios Papanicolau-Sengos and Lenzo, {Felicia L.} and Conroy, {Jeffrey M.} and Mary Nesline and Sarabjot Pabla and Glenn, {Sean T.} and Blake Burgher and Jonathan Andreas and Vincent Giamo and Moachun Qin and Yirong Wang and Lorenzo Galluzzi and Carl Morrison",

note = "Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 The Author(s). Published with license by Taylor & Francis Group, LLC.",

year = "2018",

month = dec,

day = "2",

doi = "10.1080/2162402X.2018.1460298",

language = "English",

volume = "7",

journal = "Oncoimmunology",

issn = "2162-4011",

publisher = "Landes Bioscience",

number = "12",

}

George, S, Papanicolau-Sengos, A, Lenzo, FL, Conroy, JM, Nesline, M, Pabla, S, Glenn, ST, Burgher, B, Andreas, J, Giamo, V, Qin, M, Wang, Y, Galluzzi, L & Morrison, C 2018, 'PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab', Oncoimmunology, vol. 7, no. 12, e1460298. https://doi.org/10.1080/2162402X.2018.1460298

TY - JOUR

T1 - PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

AU - George, Saby

AU - Papanicolau-Sengos, Antonios

AU - Lenzo, Felicia L.

AU - Conroy, Jeffrey M.

AU - Nesline, Mary

AU - Pabla, Sarabjot

AU - Glenn, Sean T.

AU - Burgher, Blake

AU - Andreas, Jonathan

AU - Giamo, Vincent

AU - Qin, Moachun

AU - Wang, Yirong

AU - Galluzzi, Lorenzo

AU - Morrison, Carl

PY - 2018/12/2

Y1 - 2018/12/2

N2 - 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.

AB - 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.

KW - 22C3 assay

KW - ADORA2A

KW - atezolizumab

KW - immunohistochemistry

KW - PD-1

KW - SP142 assay

UR - http://www.scopus.com/inward/record.url?scp=85047660706&partnerID=8YFLogxK

U2 - 10.1080/2162402X.2018.1460298

DO - 10.1080/2162402X.2018.1460298

M3 - Article

C2 - 30524881

AN - SCOPUS:85047660706

SN - 2162-4011

VL - 7

JO - Oncoimmunology

JF - Oncoimmunology

IS - 12

M1 - e1460298

ER -

PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this