title: Follicular Lymphoma Tregs Have a Distinct Transcription Profile Impacting Their Migration and Retention in the Malignant Lymph Node.
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.
authors.affiliation: James P. Wilmot Cancer Center, Lymphoma Biology Program, Department of Medicine University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Hristina
authors.initials: H
authors.lastname: Nedelkovska
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Rosenberg
authors.affiliation: James P. Wilmot Cancer Center, Lymphoma Biology Program, Department of Medicine University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Shannon P
authors.initials: SP
authors.lastname: Hilchey
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Ollivier
authors.initials: O
authors.lastname: Hyrien
authors.affiliation: James P. Wilmot Cancer Center, Lymphoma Biology Program, Department of Medicine University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: W Richard
authors.initials: WR
authors.lastname: Burack
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester New York, United States of America.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Quataert
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester New York, United States of America.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Baker
authors.affiliation: James P. Wilmot Cancer Center, Lymphoma Biology Program, Department of Medicine University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Mitra
authors.initials: M
authors.lastname: Azadniv
authors.affiliation: University of Rochester Genomics Research Center, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Welle
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester New York, United States of America.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: James P. Wilmot Cancer Center, Lymphoma Biology Program, Department of Medicine University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Bernstein
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D059467:Transcriptome / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D009363:Neoplasm Proteins