Format

Send to

Choose Destination
Cancer Discov. 2019 Dec 19. pii: CD-19-0680. doi: 10.1158/2159-8290.CD-19-0680. [Epub ahead of print]

Single cell transcriptome analysis reveals disease-defining T cell subsets in the tumor microenvironment of classic Hodgkin lymphoma.

Author information

1
Centre for Lymphoid Cancer, British Columbia Cancer Agency.
2
Lymphoid Cancer Research, BC Cancer Agency.
3
Deeley Research Centre, British Columbia Cancer Agency.
4
Cedars-Sinai Medical Center.
5
Centre for Lymphoid Cancer, BC Cancer Agency.
6
Terry Fox Laboratory, BC Cancer Agency.
7
Terry Fox Laboratory/Dept Pathology, BC Cancer Agency.
8
Center for Lymphoid Cancer, British Columbia Cancer.
9
Lymphoid Cancer Research, British Columbia Cancer Agency.
10
Center for Lymphoid Cancer, British Columbia Cancer Agency.
11
Deeley Research Centre, British Columbia Cancer.
12
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen.
13
Department of Molecular Oncology, British Columbia Cancer.
14
Molecular Oncology, British Columbia Cancer Research Centre.
15
Medical Oncology, British Columbia Cancer Agency.
16
Centre for Lymphoid Cancer, British Columbia Cancer.
17
Terry Fox Laboratory, BC Cancer.
18
Deeley Research Centre, BC Cancer.
19
Institute of Human Genetics, University and University Hospital of Ulm.
20
Molecular Oncology, British Columbia Cancer Agency.
21
Center for Lymphoid Cancer, British Columbia Cancer csteidl@bccancer.bc.ca.

Abstract

Hodgkin lymphoma (HL) is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of non-cancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding crosstalk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 HL tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the HL-specific immune microenvironment at single-cell resolution. Single-cell expression profiling identified a novel HL-associated subset of T cells with prominent expression of the inhibitory receptor LAG3, and functional analyses established this LAG3+ T cell population as a mediator of immunosuppression. Multiplexed spatial assessment of immune cells in the microenvironment also revealed increased LAG3+ T cells in the direct vicinity of MHC class-II deficient tumor cells. Our findings provide novel insights into TME biology and suggest new approaches to immune checkpoint targeting in HL.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center