Temporal and spatial heterogeneity of programmed cell death 1-Ligand 1 expression in malignant mesothelioma

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Programmed Cell Death 1-Ligand 1 (PD-L1) and Programmed Death Protein 1 (PD-1) blocking antibodies are promising immunotherapies for malignancies. We have previously shown PD-L1 expression in 40% of malignant mesothelioma (MM); however, the temporal and spatial heterogeneity of its expression has not been thoroughly studied. We compared PD-L1 expression between paired primary and metastatic MM. Design: Pathology files (1995–2016) were searched for MM with tissue from multiple sites and/or time points. PD-L1 (clone SP263) expression was reviewed by 2 authors. Mesothelioma cell lines (H2461, One 58, EM-MESO) were cultured with or without vinorelbine or pemetrexed. Following incubation, PD-L1 expression (clone MIH1) was analyzed by flow cytometry. Results: 64 patients (53 men, median age, 64 years) with epithelioid (N = 50), biphasic (N = 11) or sarcomatoid (N = 2) MM or well differentiated papillary mesothelioma (N = 1) (pleural, n = 56; peritoneal, n = 8) were included. Patients had a subsequent specimen from the primary site (n = 48), from a metastasis (n = 6), or both (n = 10). Reviewers agreed on PD-L1 expression in 133 of 151 (88%) specimens. There was agreement of PD-L1 expression between paired primary lesions obtained at separate time points in 47 of 58 (81%) and between paired primary and metastatic lesions in 11 of 16 (69%) cases. A significant increase in PD-L1 expression was observed in all 3 MM cell lines (p < 0.003 each) following exposure to vinorelbine but not to pemetrexed. Conclusion: Overall there is good agreement in PD-L1 expression between paired MM lesions; however, the 19–31% of cases with discordant PD-L1 expression, and the dynamics of PD-L1 expression may limit its use as a predictive biomarker for therapy.

Original languageEnglish (US)
JournalOncoImmunology
DOIs
StateAccepted/In press - Aug 19 2017

Fingerprint

CD274 Antigen
Pemetrexed
Mesothelioma
Malignant Mesothelioma
Clone Cells
Cell Line
Blocking Antibodies

Keywords

  • immunohistochemistry
  • malignant mesothelioma
  • PD-L1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

@article{c38cfe9761304f1f9e751cf3f961c3c2,
title = "Temporal and spatial heterogeneity of programmed cell death 1-Ligand 1 expression in malignant mesothelioma",
abstract = "Background: Programmed Cell Death 1-Ligand 1 (PD-L1) and Programmed Death Protein 1 (PD-1) blocking antibodies are promising immunotherapies for malignancies. We have previously shown PD-L1 expression in 40{\%} of malignant mesothelioma (MM); however, the temporal and spatial heterogeneity of its expression has not been thoroughly studied. We compared PD-L1 expression between paired primary and metastatic MM. Design: Pathology files (1995–2016) were searched for MM with tissue from multiple sites and/or time points. PD-L1 (clone SP263) expression was reviewed by 2 authors. Mesothelioma cell lines (H2461, One 58, EM-MESO) were cultured with or without vinorelbine or pemetrexed. Following incubation, PD-L1 expression (clone MIH1) was analyzed by flow cytometry. Results: 64 patients (53 men, median age, 64 years) with epithelioid (N = 50), biphasic (N = 11) or sarcomatoid (N = 2) MM or well differentiated papillary mesothelioma (N = 1) (pleural, n = 56; peritoneal, n = 8) were included. Patients had a subsequent specimen from the primary site (n = 48), from a metastasis (n = 6), or both (n = 10). Reviewers agreed on PD-L1 expression in 133 of 151 (88{\%}) specimens. There was agreement of PD-L1 expression between paired primary lesions obtained at separate time points in 47 of 58 (81{\%}) and between paired primary and metastatic lesions in 11 of 16 (69{\%}) cases. A significant increase in PD-L1 expression was observed in all 3 MM cell lines (p < 0.003 each) following exposure to vinorelbine but not to pemetrexed. Conclusion: Overall there is good agreement in PD-L1 expression between paired MM lesions; however, the 19–31{\%} of cases with discordant PD-L1 expression, and the dynamics of PD-L1 expression may limit its use as a predictive biomarker for therapy.",
keywords = "immunohistochemistry, malignant mesothelioma, PD-L1",
author = "Terra, {Simone B.S.P.} and Aaron Mansfield and Dong, {Haidong M} and Peikert, {Tobias D} and Anja Roden",
year = "2017",
month = "8",
day = "19",
doi = "10.1080/2162402X.2017.1356146",
language = "English (US)",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",

}

TY - JOUR

T1 - Temporal and spatial heterogeneity of programmed cell death 1-Ligand 1 expression in malignant mesothelioma

AU - Terra, Simone B.S.P.

AU - Mansfield, Aaron

AU - Dong, Haidong M

AU - Peikert, Tobias D

AU - Roden, Anja

PY - 2017/8/19

Y1 - 2017/8/19

N2 - Background: Programmed Cell Death 1-Ligand 1 (PD-L1) and Programmed Death Protein 1 (PD-1) blocking antibodies are promising immunotherapies for malignancies. We have previously shown PD-L1 expression in 40% of malignant mesothelioma (MM); however, the temporal and spatial heterogeneity of its expression has not been thoroughly studied. We compared PD-L1 expression between paired primary and metastatic MM. Design: Pathology files (1995–2016) were searched for MM with tissue from multiple sites and/or time points. PD-L1 (clone SP263) expression was reviewed by 2 authors. Mesothelioma cell lines (H2461, One 58, EM-MESO) were cultured with or without vinorelbine or pemetrexed. Following incubation, PD-L1 expression (clone MIH1) was analyzed by flow cytometry. Results: 64 patients (53 men, median age, 64 years) with epithelioid (N = 50), biphasic (N = 11) or sarcomatoid (N = 2) MM or well differentiated papillary mesothelioma (N = 1) (pleural, n = 56; peritoneal, n = 8) were included. Patients had a subsequent specimen from the primary site (n = 48), from a metastasis (n = 6), or both (n = 10). Reviewers agreed on PD-L1 expression in 133 of 151 (88%) specimens. There was agreement of PD-L1 expression between paired primary lesions obtained at separate time points in 47 of 58 (81%) and between paired primary and metastatic lesions in 11 of 16 (69%) cases. A significant increase in PD-L1 expression was observed in all 3 MM cell lines (p < 0.003 each) following exposure to vinorelbine but not to pemetrexed. Conclusion: Overall there is good agreement in PD-L1 expression between paired MM lesions; however, the 19–31% of cases with discordant PD-L1 expression, and the dynamics of PD-L1 expression may limit its use as a predictive biomarker for therapy.

AB - Background: Programmed Cell Death 1-Ligand 1 (PD-L1) and Programmed Death Protein 1 (PD-1) blocking antibodies are promising immunotherapies for malignancies. We have previously shown PD-L1 expression in 40% of malignant mesothelioma (MM); however, the temporal and spatial heterogeneity of its expression has not been thoroughly studied. We compared PD-L1 expression between paired primary and metastatic MM. Design: Pathology files (1995–2016) were searched for MM with tissue from multiple sites and/or time points. PD-L1 (clone SP263) expression was reviewed by 2 authors. Mesothelioma cell lines (H2461, One 58, EM-MESO) were cultured with or without vinorelbine or pemetrexed. Following incubation, PD-L1 expression (clone MIH1) was analyzed by flow cytometry. Results: 64 patients (53 men, median age, 64 years) with epithelioid (N = 50), biphasic (N = 11) or sarcomatoid (N = 2) MM or well differentiated papillary mesothelioma (N = 1) (pleural, n = 56; peritoneal, n = 8) were included. Patients had a subsequent specimen from the primary site (n = 48), from a metastasis (n = 6), or both (n = 10). Reviewers agreed on PD-L1 expression in 133 of 151 (88%) specimens. There was agreement of PD-L1 expression between paired primary lesions obtained at separate time points in 47 of 58 (81%) and between paired primary and metastatic lesions in 11 of 16 (69%) cases. A significant increase in PD-L1 expression was observed in all 3 MM cell lines (p < 0.003 each) following exposure to vinorelbine but not to pemetrexed. Conclusion: Overall there is good agreement in PD-L1 expression between paired MM lesions; however, the 19–31% of cases with discordant PD-L1 expression, and the dynamics of PD-L1 expression may limit its use as a predictive biomarker for therapy.

KW - immunohistochemistry

KW - malignant mesothelioma

KW - PD-L1

UR - http://www.scopus.com/inward/record.url?scp=85028525184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028525184&partnerID=8YFLogxK

U2 - 10.1080/2162402X.2017.1356146

DO - 10.1080/2162402X.2017.1356146

M3 - Article

AN - SCOPUS:85028525184

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

ER -