MicroRNA signatures and Foxp3+ cell count correlate with relapse occurrence in follicular lymphoma

Giorgio Malpeli, Stefano Barbi, Corinna Greco, Simonetta Zupo, Anna Bertolaso, Maria Teresa Scupoli, Mauro Krampera, Paul Takam Kamga, Carlo Maria Croce, Aldo Scarpa, Alberto Zamò

Research output: Contribution to journalArticlepeer-review

Abstract

First line drug treatment of follicular lymphoma (FL) patients is followed by a highly variable disease-free time before relapse in about one third of patients. No molecular marker is able to predict efficiently the risk of relapse. We investigated the expression profile of microRNAs (miRNAs) by microarrays and of the tumor microenvironment by immunohistochemistry in 26 FLs and 12 reactive lymph nodes (rLN) as reference. Twenty-nine miRNAs were differentially expressed in FLs compared to rLNs and some of them discriminated grade 1 from 3a FLs. Both FLs and rLNs displayed molecular heterogeneity. FLs grouped into two clusters mostly driven by the tumor T-cell content. Among 21 drug-treated FL patients with an average followup of 13.5 years, eight cases relapsed. Twenty-six miRNAs discriminated between relapsed and non-relapsed FLs. Ten miRNAs also correlated with Foxp3+ cells number. Notably, Foxp3+ cells were significantly less in relapsed patients and lower Foxp3+ cell number associated with shorter time-to-relapse. Foxp3+ cells did not co-expressed follicular helper T-cell markers and were therefore classified as regulatory T cells rather than follicular regulatory T-cells. These findings introduce new knowledge about the relationship between miRNA alterations and infiltrating immune cells and show that Foxp3+ cells might be predictive of disease relapse.

Original languageEnglish
Pages (from-to)19961-19979
Number of pages19
JournalOncotarget
Volume9
Issue number28
DOIs
Publication statusPublished - Apr 13 2018

Keywords

  • Follicular lymphoma
  • Foxp3
  • Heterogeneity
  • MicroRNAs
  • Relapse

ASJC Scopus subject areas

  • Oncology

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