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Published on: January 7, 2019
Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome
Peter Mu-Hsin Chang1, Po-Min Chen, Shie-Liang Hsieh
1Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R O C.
Abstract:
The soluble decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. It is regarded as a decoy receptor released from tumor cells to escape host immune response by neutralizing the cytotoxic and immunomodulatory effects of FasL, LIGHT and TL1A. Overexpression of DcR3 has been observed in several human malignancies; however, only limited information exists on the role of DcR3 in non-Hodgkin lymphoma especially for B-cell origin. In the current study, the expression profile of DcR3 was analyzed by RT-PCR and immunohistochemistry (IHC) in a set of lymphoma cell lines including T-cell and B-cell lymphomas. The result demonstrated that overexpression of DcR3 was detected in most T-cell lymphoma cells, which was consistent with previous reports. Interestingly, overexpression of DcR3 was also detected both in the B-cell lymphoma cell lines and diffuse large B cell lymphoma (DLBCL) patients. DcR3 overexpression was associated with a worse prognosis in DLBCL patients (p=0.05). An in vitro study showed that neutralization of DcR3 increased the percentage of doxorubicin-mediated apoptosis in two B-cell lymphoma cell lines, which indicated the possibility of DcR3 mediated chemo-resistance in B-cell lymphomas. We suggest that overexpression of DcR3 is associated with a worse prognosis in DLBCL and the possible mechanism may act through the increase of chemo-resistance of lymphoma cells.
Insights
Soluble decoy receptor 3 (DcR3) is overexpressed in B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL), and is linked to a worse prognosis. Neutralizing DcR3 may enhance chemotherapy effectiveness in these cancers.
Area of Science:
- Immunology
- Oncology
Background:
- Soluble decoy receptor 3 (DcR3), a TNF receptor superfamily member, aids tumor immune evasion.
- DcR3 overexpression is noted in malignancies, but its role in B-cell non-Hodgkin lymphoma is understudied.
Purpose of the Study:
- To investigate DcR3 expression in T-cell and B-cell lymphomas.
- To determine the prognostic significance of DcR3 in diffuse large B-cell lymphoma (DLBCL).
- To explore DcR3's role in B-cell lymphoma chemoresistance.
Main Methods:
- RT-PCR and immunohistochemistry (IHC) were used to analyze DcR3 expression in lymphoma cell lines and patient samples.
- Statistical analysis was performed to correlate DcR3 expression with DLBCL prognosis.
- In vitro studies assessed the effect of DcR3 neutralization on doxorubicin-induced apoptosis.
Main Results:
- DcR3 was overexpressed in most T-cell lymphomas and notably in B-cell lymphomas, including DLBCL.
- DcR3 overexpression correlated with a worse prognosis in DLBCL patients (p=0.05).
- Neutralizing DcR3 enhanced doxorubicin-mediated apoptosis in B-cell lymphoma cell lines.
Conclusions:
- DcR3 overexpression is associated with poor prognosis in DLBCL.
- DcR3 may contribute to chemoresistance in B-cell lymphomas, suggesting it as a potential therapeutic target.
