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

被引：22

作者：

Caggiari L. ^{[1
]}

Guidoboni M. ^{[1
]}

Vaccher E. ^{[2
]}

Barzan L. ^{[3
]}

Franchin G. ^{[4
]}

Gloghini A. ^{[5
]}

Martorelli D. ^{[1
]}

Zancai P. ^{[1
]}

Bortolin M.T. ^{[8
]}

Mazzucato M. ^{[6
]}

Serraino D. ^{[1
]}

Carbone A. ^{[7
]}

De Paoli P. ^{[8
]}

Dolcetti R. ^{[1
,9
]}

机构：

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

[2] Dept. of Medical Oncology, Centro di Riferimento Oncologico, IRCCS - National Cancer Institute, Aviano (PN)

[3] Head and Neck Department, Azienda Ospedaliera, Pordenone

[4] Dept. of Radiotherapy, Centro di Riferimento Oncologico, IRCCS - National Cancer Institute, Aviano (PN)

[5] Dept. of Pathology, Diagnostic Immunohistochemistry and Molecular Pathology Unit, IRCCS - National Cancer Institute, Aviano (PN)

[6] Blood Bank, Centra di Riferimento Oncologico, IRCCS - National Cancer Institute, Aviano (PN)

[7] Dept. of Pathology, Istituto Nazionale Tumori, Milan

[8] Microbiology Unit, Centro di Riferimento Oncologico, IRCCS - National Cancer Institute, Aviano (PN)

[9] Immunovirology and Biotherapy Unit, Centro di Riferimento Oncologico, National Cancer Institute, 33081, Aviano (PN)

来源：

Infectious Agents and Cancer | / 2卷 / 1期

关键词：

Active Thrombin; CD40 Activation; Regional Lymph Node Involvement; CD40L Expression; sCD40L Level;

D O I：

10.1186/1750-9378-2-5

中图分类号：

学科分类号：

摘要：

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.

引用

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