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Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphoma

Lookup NU author(s): Dr Christopher CareyORCiD

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Society of Hematology, 2017.

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Abstract

© 2017 by The American Society of Hematology. Signaling between programmed cell death protein 1 (PD-1) and the PD-1 ligands (PD-L1, PD-L2) is essential for malignant Hodgkin Reed-Sternberg (HRS) cells to evade antitumor immunity in classical Hodgkin lymphoma (cHL). Copy number alterations of 9p24.1/ CD274(PD-L1)/PDCD1LG2 (PD-L2) contribute to robust PD-L1 and PD-L2 expression by HRS cells. PD-L1 is also expressed by nonmalignant tumor-associated macrophages (TAMs), but the relationships among PD-L11 HRS cells, PD-L11 TAMs, and PD-11 T cells remain undefined. We used multiplex immunofluorescence and digital image analysis to examine the topography of PD-L11 and PD-11 cells in the tumor microenvironment (TME) of cHL. We find that the majority of PD-L1 in the TME is expressed by the abundant PD-L11 TAMs, which physically colocalize with PD-L11 HRS cells in a microenvironmental niche. PD-L11 TAMs are enriched for contacts with T cells, and PD-L11 HRS cells are enriched for contacts with CD41 T cells, a subset of which are PD-11. Our data define a unique topology of cHL in which PD-L11 TAMs surround HRS cells and implicate CD41 T cells as a target of PD-1 blockade.

Publication metadata

Author(s): Carey CD, Gusenleitner D, Lipschitz M, Roemer MGM, Stack EC, Gjini E, Hu X, Redd R, Freeman GJ, Neuberg D, Hodi FS, Liu XS, Shipp MA, Rodig SJ

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2017

Volume: 130

Issue: 22

Pages: 2420-2430

Print publication date: 30/11/2017

Online publication date: 30/11/2017

Acceptance date: 18/08/2017

Date deposited: 27/02/2018

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology

URL: https://doi.org/10.1182/blood-2017-03-770719

DOI: 10.1182/blood-2017-03-770719

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