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Article: Phenotype, Function, and Clinical Significance of CD26+ and CD161+Tregs in Splenic Marginal Zone Lymphoma

TitlePhenotype, Function, and Clinical Significance of CD26+ and CD161+Tregs in Splenic Marginal Zone Lymphoma
Authors
Issue Date9-Jun-2022
PublisherAmerican Association for Cancer Research
Citation
Clinical Cancer Research, 2022, v. 28, n. 19, p. 4322-4335 How to Cite?
Abstract

Purpose:

Regulatory T-cells (Treg) are essential to Tregs homeostasis and modulate the antitumor immune response in patients with lymphoma. However, the biology and prognostic impact of Tregs in splenic marginal zone lymphoma (SMZL) have not been studied.

Experimental Design:

Biopsy specimens from 24 patients with SMZL and 12 reactive spleens (rSP) from individuals without lymphoma were analyzed by using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), CyTOF (mass cytometry) analysis, and flow cytometry to explore the phenotype, transcriptomic profile, and clinical significance of intratumoral Tregs and their subsets. The biological characteristics and cell signaling pathways of intratumoral Treg subsets were confirmed by in vitro functional assays.

Results:

We found that Tregs are more abundant in SMZL patients' spleens than rSP, and Tregs from patients with SMZL and rSP can be separated into CD161+Treg and CD26+Treg subsets. CD161+Tregs are increased in SMZL but have dysregulated immune function. We found that CD161+Treg and CD26+Tregs have unique gene expression and phenotypic profiles and are differentially correlated with patient outcomes. Specifically, increased CD161+Tregs are significantly associated with a favorable prognosis in patients with SMZL, whereas CD26+Tregs are associated with a poor prognosis. Furthermore, activation of the IL2/STAT5 pathway contributes to the induction of CD26+Tregs and can be reversed by STAT5 inhibition.

Conclusions:

IL2/STAT5-mediated expansion of CD26+Tregs contributes to a poor clinical outcome in SMZL and may represent a therapeutic opportunity in this disease.


Persistent Identifierhttp://hdl.handle.net/10722/331524
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTang, XY-
dc.contributor.authorYang, ZZ-
dc.contributor.authorKim, HJ-
dc.contributor.authorAnagnostou, T-
dc.contributor.authorYu, Y-
dc.contributor.authorWu, XS-
dc.contributor.authorChen, J-
dc.contributor.authorKrull, JE-
dc.contributor.authorWenzl, K-
dc.contributor.authorMondello, P-
dc.contributor.authorBhardwaj, V-
dc.contributor.authorWang, JW-
dc.contributor.authorNovak, AJ-
dc.contributor.authorAnsell, SM-
dc.date.accessioned2023-09-21T06:56:36Z-
dc.date.available2023-09-21T06:56:36Z-
dc.date.issued2022-06-09-
dc.identifier.citationClinical Cancer Research, 2022, v. 28, n. 19, p. 4322-4335-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/331524-
dc.description.abstract<p>Purpose:</p><p>Regulatory T-cells (Treg) are essential to Tregs homeostasis and modulate the antitumor immune response in patients with lymphoma. However, the biology and prognostic impact of Tregs in splenic marginal zone lymphoma (SMZL) have not been studied.</p><p>Experimental Design:</p><p>Biopsy specimens from 24 patients with SMZL and 12 reactive spleens (rSP) from individuals without lymphoma were analyzed by using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), CyTOF (mass cytometry) analysis, and flow cytometry to explore the phenotype, transcriptomic profile, and clinical significance of intratumoral Tregs and their subsets. The biological characteristics and cell signaling pathways of intratumoral Treg subsets were confirmed by <em>in vitro</em> functional assays.</p><p>Results:</p><p>We found that Tregs are more abundant in SMZL patients' spleens than rSP, and Tregs from patients with SMZL and rSP can be separated into CD161<sup>+</sup>Treg and CD26<sup>+</sup>Treg subsets. CD161<sup>+</sup>Tregs are increased in SMZL but have dysregulated immune function. We found that CD161<sup>+</sup>Treg and CD26<sup>+</sup>Tregs have unique gene expression and phenotypic profiles and are differentially correlated with patient outcomes. Specifically, increased CD161<sup>+</sup>Tregs are significantly associated with a favorable prognosis in patients with SMZL, whereas CD26<sup>+</sup>Tregs are associated with a poor prognosis. Furthermore, activation of the IL2/STAT5 pathway contributes to the induction of CD26<sup>+</sup>Tregs and can be reversed by STAT5 inhibition.</p><p>Conclusions:</p><p>IL2/STAT5-mediated expansion of CD26<sup>+</sup>Tregs contributes to a poor clinical outcome in SMZL and may represent a therapeutic opportunity in this disease.</p>-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofClinical Cancer Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titlePhenotype, Function, and Clinical Significance of CD26+ and CD161+Tregs in Splenic Marginal Zone Lymphoma-
dc.typeArticle-
dc.identifier.doi10.1158/1078-0432.CCR-22-0977-
dc.identifier.scopuseid_2-s2.0-85139521792-
dc.identifier.volume28-
dc.identifier.issue19-
dc.identifier.spage4322-
dc.identifier.epage4335-
dc.identifier.eissn1557-3265-
dc.identifier.isiWOS:000870526400001-
dc.identifier.issnl1078-0432-

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