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

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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 agematched 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 IMP-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.

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Caggiari, L., Guidoboni, M., Vaccher, E., Barzan, L., Franchin, G., Gloghini, A., … Dolcetti, R. (2007). High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: Pathogenic and clinical relevance. Infectious Agents and Cancer, 2(1). https://doi.org/10.1186/1750-9378-2-5

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