Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

Luigi Maria Larocca, Stefan Hohaus, Camille Laurent, Sabina Müller, Catherine Do, Talal Al-Saati, Sophie Allart, Sophie Duchez, Anne Quillet-Mary, Guy Laurent, Pierre Brousset, Salvatore Valitutti

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

50 Citazioni (Scopus)

Abstract

CD8+ CTLs are thought to play a role in the control of follicular lymphoma (FL). Yet, the link between CTL tissue distribution, activation status, ability to kill FL cells in vivo, and disease progression is still elusive. Pretreatment lymph nodes from FL patients were analyzed by IHC (n = 80) or by 3-color confocal microscopy (n = 10). IHC revealed a rich infiltrate of CD8+ granzyme B+ (GrzB) cells in FL interfollicular spaces. Accordingly, confocal microscopy showed an increased number of CD3+CD8+GrzB+ CTLs and a brighter GrzB staining in individual CTL in FL samples compared with reactive lymph nodes. CTLs did not penetrate tumor nodules. In 3-dimensional (3-D) image reconstructions, CTLs were detected at the FL follicle border where they formed lytic synapse-like structures with FL B cells and with apoptotic cells, suggesting an in situ cytotoxic function. Finally, although GrzB expression in CTLs did not correlate with risk factors, high GrzB content correlated with prolonged progression free-survival (PFS) after rituximab-combined chemotherapy. Our results show the recruitment of armed CTLs with a tumor-controlling potential into FL lymph nodes and suggest that CTL-associated GrzB expression could influence PFS in FL patients having received rituximab-combined chemotherapy.
Lingua originaleEnglish
pagine (da-a)5371-5379
Numero di pagine9
RivistaBlood
Volume118
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD3
  • Antigens, CD8
  • Antineoplastic Combined Chemotherapy Protocols
  • Cyclophosphamide
  • Doxorubicin
  • Female
  • Granzymes
  • Humans
  • Imaging, Three-Dimensional
  • Lymph Nodes
  • Lymphoma, Follicular
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Predictive Value of Tests
  • Prednisone
  • Prognosis
  • Risk Factors
  • T-Lymphocytes, Cytotoxic
  • Tumor Markers, Biological
  • Vincristine

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