title: High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance.
abstract: BACKGROUND
  Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease.
  
  
  RESULTS
  At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L+ lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass.
  
  
  CONCLUSIONS
  sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation.
authors.affiliation: Dept of Pre-Clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano (PN), Italy. lcaggiari@cro.it
authors.forename: Laura
authors.initials: L
authors.lastname: Caggiari
authors.forename: Massimo
authors.initials: M
authors.lastname: Guidoboni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Vaccher
authors.forename: Luigi
authors.initials: L
authors.lastname: Barzan
authors.forename: Giovanni
authors.initials: G
authors.lastname: Franchin
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.forename: Debora
authors.initials: D
authors.lastname: Martorelli
authors.forename: Paola
authors.initials: P
authors.lastname: Zancai
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bortolin
authors.forename: Mario
authors.initials: M
authors.lastname: Mazzucato
authors.forename: Diego
authors.initials: D
authors.lastname: Serraino
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Paolo
authors.initials: P
authors.lastname: De Paoli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti