Abstract
Chronic hepatitis B (CHB) has been reported to be associated with impaired prognosis for patients with nasopharyngeal carcinoma (NPC). However, the latent mechanism is unclear. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) induce immune suppression in CHB and promote the development of hepatocellular carcinoma. Lectin-type oxidized LDL receptor-1 (LOX-1) was recently identified as a specific marker for PMN-MSDC. We found NPC survivors with CHB had high levels of LOX-1+ PMN-MDSCs. LOX-1+ PMN-MDSCs significantly reduced T cell proliferation and activation. Endoplasmic reticulum stress was induced in LOX-1+ PMN-MDSCs. In addition, LOX-1+ PMN-MDSCs increased their expression of NOX2, a key reactive oxygen species (ROS)-related genes, and levels of ROS illustrated by the DCFDA test. The ROS inhibitor N-acetylcysteine abrogated the suppression of LOX-1+ PMN-MDSCs on T cell activation. The EBV DNA-positivity rate was higher in NPC survivors with CHB than in NPC patients without CHB. Those presenting with positive EBV DNA displayed higher LOX-1+ PMN-MDSC levels. LOX-1+ PMN-MDSCs suppressed the CD8+ T cell response against EBV. This study revealed LOX-1+ PMN-MDSC accumulation and activation in NPC survivors with CHB. LOX-1+ PMN-MDSCs might suppress the host immune response to EBV through ER stress/ROS pathway. These results explained the association of CHB with unfavorable NPC prognosis.
Highlights
Nasopharyngeal carcinoma (NPC) has an unbalanced geographical global distribution and is one of the major malignancies in East and Southeast Asia [1]
We found that Chronic hepatitis B (CHB) promoted LDL receptor-1 (LOX-1)+ PMN-MDSC expansion and activation in nasopharyngeal carcinoma (NPC) survivors, and that LOX-1+ PMNMDSCs may permit Epstein–Barr virus (EBV) immune tolerance
These results indicated that LOX-1+ PMN-MDSC mediated CHB induced NPC recurrence
Summary
Nasopharyngeal carcinoma (NPC) has an unbalanced geographical global distribution and is one of the major malignancies in East and Southeast Asia [1]. The mechanism of NPC tumor recurrence is receiving close attention in this field [3]. Non-keratinizing cancer is the major pathological subtype of NPC in epidemic areas (95%) and is predominantly associated with Epstein–Barr virus (EBV) infection [1], which is perhaps the most common causal agent of NPC [4]. Hepatitis B virus (HBV) is another virus related to NPC [7,8,9], and in the last decade has reached epidemic levels in East and Southeast Asia [10]. Our previous study found that HBV infection was associated with impaired prognosis of NPC patients [11].
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