PD-1/PD-L1 expression and interaction by automated quantitative immunofluorescent analysis show adverse prognostic impact in patients with diffuse large B-cell lymphoma having T-cell infiltration: a study from the International DLBCL Consortium Program.

dc.contributor.author

Li, Ling

dc.contributor.author

Sun, Ruifang

dc.contributor.author

Miao, Yi

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Tran, Thai

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Adams, Lisa

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Roscoe, Nathan

dc.contributor.author

Xu, Bing

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Manyam, Ganiraju C

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Tan, Xiaohong

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Zhang, Hongwei

dc.contributor.author

Xiao, Min

dc.contributor.author

Tzankov, Alexandar

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Visco, Carlo

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Dybkaer, Karen

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Bhagat, Govind

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Tam, Wayne

dc.contributor.author

Hsi, Eric D

dc.contributor.author

van Krieken, J Han

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You, Hua

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Huh, Jooryung

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Ponzoni, Maurilio

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Ferreri, Andrés JM

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Møller, Michael B

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Piris, Miguel A

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Zhang, Mingzhi

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Winter, Jane N

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Medeiros, L Jeffrey

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Rassidakis, George Z

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Vaupel, Christine A

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Li, Yong

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Dakappagari, Naveen

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Xu-Monette, Zijun Y

dc.contributor.author

Young, Ken H

dc.date.accessioned

2019-09-21T21:26:42Z

dc.date.available

2019-09-21T21:26:42Z

dc.date.issued

2019-06

dc.date.updated

2019-09-21T21:26:41Z

dc.description.abstract

Programmed cell death protein 1/programmed cell death protein ligand1 (PD-1/PD-L1) interaction is an important immune checkpoint targeted by anti-PD-1/PD-L1 immunotherapies. However, the observed prognostic significance of PD-1/PD-L1 expression in diffuse large B-cell lymphoma treated with the standard of care has been inconsistent and even contradictory. To clarify the prognostic role of PD-1/PD-L1 expression and interaction in diffuse large B-cell lymphoma, in this study we used 3-marker fluorescent multiplex immunohistochemistry and Automated Quantitative Analysis Technology to assess the CD3+, PD-L1+, and PD-1+CD3+ expression in diagnostic samples and PD-1/PD-L1 interaction as indicated by presence of PD-1+CD3+ cells in the vicinity of PD-L1+ cells, analyzed their prognostic effects in 414 patients with de novo diffuse large B-cell lymphoma, and examined whether PD-1/PD-L1 interaction is required for the prognostic role of PD-1+/PD-L1+ expression. We found that low T-cell tissue cellularity, tissue PD-L1+ expression (irrespective of cell types), PD-1+CD3+ expression, and PD-1/PD-L1 interaction showed hierarchical adverse prognostic effects in the study cohort. PD-1/PD-L1 interaction showed higher sensitivity and specificity than PD-1+ and PD-L1+ expression in predicting inferior prognosis in patients with high CD3+ tissue cellularity ("hot"/inflammatory tumors). However, both PD-1+ and PD-L1+ expression showed adverse prognostic effects independent of PD-1/PD-L1 interaction, and PD-1/PD-L1 interaction showed favorable prognostic effect in PD-L1+ patients without high CD3+ tissue cellularity. Macrophage function and tumor-cell MYC expression may contribute to the PD-1-independent adverse prognostic effect of PD-L1+ expression. In summary, low T-cell tissue cellularity has unfavorable prognostic impact in diffuse large B-cell lymphoma, and tissue PD-L1+ expression and T-cell-derived PD-1+ expression have significant adverse impact only in patients with high T-cell infiltration. PD-1/PD-L1 interaction in tissue is essential but not always responsible for the inhibitory effect of PD-L1+/PD-1+ expression. These results suggest the benefit of PD-1/PD-L1 blockade therapies only in patients with sufficient T-cell infiltration, and the potential of immunofluorescent assays and Automated Quantitative Analysis in the clinical assessment of PD-1/PD-L1 expression and interaction.

dc.identifier

10.1038/s41379-018-0193-5

dc.identifier.issn

0893-3952

dc.identifier.issn

1530-0285

dc.identifier.uri

https://hdl.handle.net/10161/19335

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

dc.relation.isversionof

10.1038/s41379-018-0193-5

dc.subject

Science & Technology

dc.subject

Life Sciences & Biomedicine

dc.subject

Pathology

dc.subject

DEATH-LIGAND 1

dc.subject

PD-1 BLOCKADE

dc.subject

RITUXIMAB

dc.subject

SURVIVAL

dc.subject

HODGKIN

dc.subject

PHAGOCYTOSIS

dc.subject

MACROPHAGES

dc.subject

ENGAGEMENT

dc.subject

CANCER

dc.subject

MEMBER

dc.title

PD-1/PD-L1 expression and interaction by automated quantitative immunofluorescent analysis show adverse prognostic impact in patients with diffuse large B-cell lymphoma having T-cell infiltration: a study from the International DLBCL Consortium Program.

dc.type

Journal article

duke.contributor.orcid

Xu-Monette, Zijun Y|0000-0002-7615-3949

duke.contributor.orcid

Young, Ken H|0000-0002-5755-8932

pubs.begin-page

741

pubs.end-page

754

pubs.issue

6

pubs.organisational-group

School of Medicine

pubs.organisational-group

Duke

pubs.organisational-group

Pathology

pubs.organisational-group

Clinical Science Departments

pubs.publication-status

Published

pubs.volume

32

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