Single-cell analysis can define distinct evolution of tumor sites in follicular lymphoma.
Adult
Aged
Antigens, Neoplasm
/ biosynthesis
Biopsy, Fine-Needle
CD40 Antigens
/ biosynthesis
CD40 Ligand
/ biosynthesis
Clonal Evolution
/ genetics
DNA, Neoplasm
/ genetics
Disease Progression
Female
Flow Cytometry
Gene Rearrangement, B-Lymphocyte, Light Chain
Gene Rearrangement, T-Lymphocyte
Humans
Lymph Nodes
/ chemistry
Lymphocytes, Tumor-Infiltrating
/ immunology
Lymphoma, Follicular
/ chemistry
Male
Middle Aged
Neoplasm Proteins
/ biosynthesis
Phylogeny
RNA, Neoplasm
/ genetics
Sequence Alignment
Sequence Homology, Nucleic Acid
Single-Cell Analysis
T Follicular Helper Cells
/ immunology
Transcriptome
Tumor Microenvironment
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
27 05 2021
27 05 2021
Historique:
received:
09
11
2020
accepted:
11
02
2021
pubmed:
18
3
2021
medline:
15
12
2021
entrez:
17
3
2021
Statut:
ppublish
Résumé
Tumor heterogeneity complicates biomarker development and fosters drug resistance in solid malignancies. In lymphoma, our knowledge of site-to-site heterogeneity and its clinical implications is still limited. Here, we profiled 2 nodal, synchronously acquired tumor samples from 10 patients with follicular lymphoma (FL) using single-cell RNA, B-cell receptor (BCR) and T-cell receptor sequencing, and flow cytometry. By following the rapidly mutating tumor immunoglobulin genes, we discovered that BCR subclones were shared between the 2 tumor sites in some patients, but in many patients, the disease had evolved separately with limited tumor cell migration between the sites. Patients exhibiting divergent BCR evolution also exhibited divergent tumor gene-expression and cell-surface protein profiles. While the overall composition of the tumor microenvironment did not differ significantly between sites, we did detect a specific correlation between site-to-site tumor heterogeneity and T follicular helper (Tfh) cell abundance. We further observed enrichment of particular ligand-receptor pairs between tumor and Tfh cells, including CD40 and CD40LG, and a significant correlation between tumor CD40 expression and Tfh proliferation. Our study may explain discordant responses to systemic therapies, underscores the difficulty of capturing a patient's disease with a single biopsy, and furthers our understanding of tumor-immune networks in FL.
Identifiants
pubmed: 33728464
pii: S0006-4971(21)00690-X
doi: 10.1182/blood.2020009855
pmc: PMC8160505
doi:
Substances chimiques
Antigens, Neoplasm
0
CD40 Antigens
0
DNA, Neoplasm
0
Neoplasm Proteins
0
RNA, Neoplasm
0
CD40 Ligand
147205-72-9
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2869-2880Subventions
Organisme : NCI NIH HHS
ID : K08 CA252637
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197353
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 by The American Society of Hematology.
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