Neuropilin-1 expression identifies a subset of regulatory T cells in human lymph nodes that is modulated by preoperative chemoradiation therapy in cervical cancer

Alessandra Battaglia, Alexia Buzzonetti, Giovanni Monego, Laura Peri, Gabriella Ferrandina, Francesco Fanfani, Giovanni Scambia, Andrea Fattorossi

Research output: Contribution to journalArticle

Abstract

We examined the phenotype and function of CD4+ T cells expressing the semaphorin III receptor neuropilin-1 (Nrp1) in human lymph nodes and peripheral blood. In lymph nodes, Nrp1 identified a small regulatory CD4+ CD25high T-cell subpopulation (Nrp1+ Treg) that expressed higher levels of Forkhead box P3 (Foxp3) message and protein than Nrp1- Treg, and various molecular markers of activated Treg, i.e. CD45RO, human leucocyte antigen (HLA)-DR and glucocorticoid-induced tumour necrosis factor receptor (GITR). Similarly to conventional Treg, Nrp1 + Treg proliferated poorly in vitro, and exerted contact-dependent in vitro suppression of T-cell proliferation and cytokine secretion. However, Nrp1+ Treg were more efficient than Nrp1- Treg at inducing suppression. Nrp1 was also expressed on a small subpopulation of CD25 int and CD25- CD4+ T cells that expressed more Foxp3, CD45RO, HLA-DR and GITR than their Nrp1- counterparts. In contrast, in peripheral blood Nrp1 identified a minor CD4+ T-cell subset that did not display the phenotypic features of Treg lacking Foxp3 expression and marginally expressing CD25. Hence, the function of Nrp1 + CD4+ T cells seemingly depends on their anatomical location. In a previous report, we proposed that Treg may curb the anti-tumour T-cell response in cervical cancer. We show here that Treg and Nrp1+ Treg levels dropped in the tumour-draining lymph nodes of patients with cervical cancer following preoperative chemoradiotherapy in a direct relationship with the reduction of tumour mass, suggesting that suppressor cell elimination facilitated the generation of T cells mediating the destruction of the neoplastic cells left behind after cytotoxic therapy.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalImmunology
Volume123
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • Cervical cancer
  • Chemoradiation
  • Human lymph node
  • Neuropilin-1
  • Regulatory T cell

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Neuropilin-1 expression identifies a subset of regulatory T cells in human lymph nodes that is modulated by preoperative chemoradiation therapy in cervical cancer'. Together they form a unique fingerprint.

  • Cite this