Open Access Research article

High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

Laura Caggiari1, Massimo Guidoboni1, Emanuela Vaccher2, Luigi Barzan3, Giovanni Franchin4, Annunziata Gloghini5, Debora Martorelli1, Paola Zancai1, Maria Teresa Bortolin8, Mario Mazzucato6, Diego Serraino1, Antonino Carbone7, Paolo De Paoli8 and Riccardo Dolcetti19*

Author Affiliations

1 Dept. of Pre-Clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS – National Cancer Institute, Aviano (PN), Italy

2 Dept. of Medical Oncology, Centro di Riferimento Oncologico, IRCCS – National Cancer Institute, Aviano (PN), Italy

3 Head and Neck Department, Azienda Ospedaliera, Pordenone, Italy

4 Dept. of Radiotherapy, Centro di Riferimento Oncologico, IRCCS – National Cancer Institute, Aviano (PN), Italy

5 Dept. of Pathology, Diagnostic Immunohistochemistry and Molecular Pathology Unit, Centro di Riferimento Oncologico, IRCCS – National Cancer Institute, Aviano (PN), Italy

6 Blood Bank, Centro di Riferimento Oncologico, IRCCS – National Cancer Institute, Aviano (PN), Italy

7 Dept. of Pathology, Istituto Nazionale Tumori, Milan, Italy

8 Microbiology Unit, Centro di Riferimento Oncologico, IRCCS – National Cancer Institute, Aviano (PN), Italy

9 Immunovirology and Biotherapy Unit, Centro di Riferimento Oncologico, National Cancer Institute, Via Franco Gallini 2, 33081, Aviano (PN), Italy

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Infectious Agents and Cancer 2007, 2:5  doi:10.1186/1750-9378-2-5

Published: 1 March 2007

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.

Conclusion

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.