Follicular lymphoma tregs have a distinct transcription profile impacting their migration and retention in the malignant lymph node

Hristina Nedelkovska, Alexander F. Rosenberg, Shannon P. Hilchey, Ollivier Hyrien, W. Richard Burack, Sally A. Quataert, Christina M. Baker, Mitra Azadniv, Stephen L. Welle, Stephen Maxted Ansell, Minsoo Kim, Steven H. Bernstein

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We have previously shown that regulatory T cells (Tregs) infiltrating follicular lymphoma lymph nodes are quantitatively and qualitatively different than those infiltrating normal and reactive nodes. To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of follicular lymphoma nodal tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin) and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of the chemokine receptor CXCR5 as well as the secretion of the chemokines CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how follicular lymphoma nodal Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets.

Original languageEnglish (US)
Article numbere0155347
JournalPLoS One
Volume11
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Chemokine CXCL13
Interleukin-16
L-Selectin
Follicular Lymphoma
T-cells
Chemokine Receptors
Transcription
lymphoma
Interleukin-10
lymph nodes
Tumors
transcription (genetics)
Lymph Nodes
Cells
RNA
Molecules
Proteins
Up-Regulation
RNA Sequence Analysis
Tumor Microenvironment

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Nedelkovska, H., Rosenberg, A. F., Hilchey, S. P., Hyrien, O., Burack, W. R., Quataert, S. A., ... Bernstein, S. H. (2016). Follicular lymphoma tregs have a distinct transcription profile impacting their migration and retention in the malignant lymph node. PLoS One, 11(5), [e0155347]. https://doi.org/10.1371/journal.pone.0155347

Follicular lymphoma tregs have a distinct transcription profile impacting their migration and retention in the malignant lymph node. / Nedelkovska, Hristina; Rosenberg, Alexander F.; Hilchey, Shannon P.; Hyrien, Ollivier; Burack, W. Richard; Quataert, Sally A.; Baker, Christina M.; Azadniv, Mitra; Welle, Stephen L.; Ansell, Stephen Maxted; Kim, Minsoo; Bernstein, Steven H.

In: PLoS One, Vol. 11, No. 5, e0155347, 01.05.2016.

Research output: Contribution to journalArticle

Nedelkovska, H, Rosenberg, AF, Hilchey, SP, Hyrien, O, Burack, WR, Quataert, SA, Baker, CM, Azadniv, M, Welle, SL, Ansell, SM, Kim, M & Bernstein, SH 2016, 'Follicular lymphoma tregs have a distinct transcription profile impacting their migration and retention in the malignant lymph node', PLoS One, vol. 11, no. 5, e0155347. https://doi.org/10.1371/journal.pone.0155347
Nedelkovska, Hristina ; Rosenberg, Alexander F. ; Hilchey, Shannon P. ; Hyrien, Ollivier ; Burack, W. Richard ; Quataert, Sally A. ; Baker, Christina M. ; Azadniv, Mitra ; Welle, Stephen L. ; Ansell, Stephen Maxted ; Kim, Minsoo ; Bernstein, Steven H. / Follicular lymphoma tregs have a distinct transcription profile impacting their migration and retention in the malignant lymph node. In: PLoS One. 2016 ; Vol. 11, No. 5.
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