| Title: |
Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphoma |
| Authors: |
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 |
| Source: |
Blood, 30 November 2017 |
| Publisher Information: |
American Society of Hematology |
| Publication Year: |
2017 |
| Collection: |
Newcastle University Library ePrints Service |
| Description: |
© 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://eprints.ncl.ac.uk/243951; https://eprints.ncl.ac.uk/fulltext.aspx?url=243951/C531DDD8-7F5B-4669-8DC0-E30F72A6781A.pdf&pub_id=243951 |
| Availability: |
https://eprints.ncl.ac.uk/243951 |
| Accession Number: |
edsbas.BBEE1817 |
| Database: |
BASE |