Abstract
Background Tumor immunotherapy and immunological checkpoint-related proteins are research hotspots. Intensity-modulated radiotherapy (IMRT) is the main treatment for nasopharyngeal carcinoma (NPC). Hence, the evaluation of its effect is very important. The aim of this study was to assess the relationship between the concentrations of soluble checkpoint proteins, plasma EBV-DNA, and cytokines in NPC patients treated with IMRT. Methods In this study, the plasma samples of 37 NPC patients and 40 healthy controls were collected. Luminex MAGPIX was used to detect the concentrations of 32 plasma targets, including soluble programmed cell death 1 (sPD-1). RT-qPCR was used to measure EBV-DNA. Results The concentrations of 33 plasma targets were detected in NPC patients before and after IMRT to explore the changes after IMRT. The results showed that IMRT could increase the expression of sPD-1 and significantly reduce the level of EBV-DNA in the plasma of NPC patients. The expression level of sPD-1 in TNM I/II patients was significantly higher than that in III/IV patients. Besides, the concentrations of 12 other targets were significantly different after IMRT, including LAG-3, PD-L1, TIM-3, IFN-γ, IL-12p70, IL-1β, IL-5, IL-6, TNF-α, IL-10, IL-17A, and IL-22. High sPD-1 patients had longer survival than those with low sPD-1. Also, patients with lower EBV-DNA and TNM grades I and II/III had longer survival than those with higher EBV-DNA or TNM IV. Conclusions This study demonstrated that the concentration of sPD-1 was significantly increased and EBV-DNA was significantly reduced in the NPC patients after IMRT. Plasma EBV-DNA level was a highly specific and sensitive biomarker for NPC diagnosis. Both sPD-1 expression and EBV-DNA concentration in plasma were related to the survival of patients.
Highlights
Nasopharyngeal carcinoma (NPC) is a malignant tumor of the upper and lateral wall of the nasopharyngeal cavity, which exhibits marked racial and geographical differences
This study demonstrated that the concentration of soluble programmed cell death 1 (sPD-1) was significantly increased and Epstein-Barr virus (EBV)-DNA was significantly reduced in the nasopharyngeal carcinoma (NPC) patients after Intensity-modulated radiotherapy (IMRT)
Plasma proteins and cytokines were compared between NPC patients before IMRT and healthy controls, and the results showed that 24 out of 32 plasma proteins and cytokines had statistical significance (Table 2), namely, BTLA (p≤ . ), GITR (p=0.022), HVEM (p≤ . ), LAG-3 (p≤ . ), sPD-1 (p≤ . ), sPD-L1 (p≤ . ), sPD-L2 (p≤ . ), CD28 (p≤ . ), CD80 (p≤ . ), CD137 (p≤ . ), CD27 (p=0.049), CD152 (p=0.002), IFN-γ (p≤ . ), IL-12p70 (p≤ . ), IL-1β (p=0.002), IL-2 (p=0.027), IL-5 (p≤ . ), IL-6 (p≤ . ), TNF-α (p≤ . ), IL-10 (p≤ . ), IL-17A (p≤ . ), IL-22 (p≤ . ), IL-27 (p≤ . ), and IL-9 (p≤ . ) (Figure 1)
Summary
Nasopharyngeal carcinoma (NPC) is a malignant tumor of the upper and lateral wall of the nasopharyngeal cavity, which exhibits marked racial and geographical differences. High plasma soluble CD40 ligand (sCD40L) level was significantly related to stage progression and poor survival of NPC patients [4]. The aim of this study was to assess the relationship between the concentrations of soluble checkpoint proteins, plasma EBV-DNA, and cytokines in NPC patients treated with IMRT. The results showed that IMRT could increase the expression of sPD-1 and significantly reduce the level of EBV-DNA in the plasma of NPC patients. This study demonstrated that the concentration of sPD-1 was significantly increased and EBV-DNA was significantly reduced in the NPC patients after IMRT. Plasma EBV-DNA level was a highly specific and sensitive biomarker for NPC diagnosis. Both sPD-1 expression and EBV-DNA concentration in plasma were related to the survival of patients
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