Exploring The Influence Of The Distribution Of Peripheral Blood Cell Immune Subgroups On The Prognosis Of Patients With Nasopharyngeal Carcinoma

Objective:This study aims to explore the clinical predictive value of the distribution of peripheral blood immune cell subsets in patients with nasopharyngeal carcinoma(NPC)and the significance of the factors that affect the changes in circulating immune cell subsets.Mainly aimed at the clinical prognosis of peripheral blood innate immune cells and peripheral blood adaptive immune cells in patients with nasopharyngeal carcinoma before treatment,and the correlation analysis with Epstein-Barr virus(EBV)DNA load.And further explore whether the commonly used clinical immune activation drug thymalfasin is beneficial to the activation of peripheral blood circulating immune cell subsets and the survival of nasopharyngeal carcinoma patients.Methods:The subjects included in this study were initially treated NPC patients with no distant metastasis in Sichuan Cancer Hospital from January2016 to October 2019.Basic data of the patients were collected and followed up through outpatient clinics and telephone.Before treatment,EBV DNA in peripheral blood was detected by real-time PCR,and the circulating immune cell subsets in peripheral blood were analyzed by flow cytometry.The receiver operating curve and Youden index analysis in medical statistical software were used to determine the parameter cut-off value of each circulating immune cell subpopulation with the greatest sensitivity and specificity to the prognosis.Survival analysis was performed using SPSS 23.0 statistical software:whether the thymalfasin affects the changes in peripheral blood circulating immune cell subsets before and after treatment in NPC patients was analyzed by paired t-test;Kaplan-Meier method was used to calculate overall survival,progression-free survival,local recurrence-free survival,and distant metastasis-free survival rate.The COX regression model conducts multivariate analysis to determine the independent predictors that affect the prognosis of NPC patients.Results:1.The deadline for follow-up is October 2020,the ratio of CD3~+T cells,CD3~+CD4~+T cells,CD3~+CD8~+T cells and CD56~+NK cells and the ratio of CD4+/CD8+did not find a suitable threshold.Single factor analysis has no obvious significance for the prognosis.The Cut-off value of the proportion of CD19+B cells is 8.33%.The patient’s 3-year OS,PFS,DMFS and LRFS with the ratio of CD19~+B cells≤8.33%and>8.33%were respectively 90.4%vs.99.2%(P=0.003),89.2%vs.97.5%(P=0.008),90.4%vs.98.3%(P=0.008),98.8%and 99.2%(P>0.05).2.The patients are divided into 2 groups according to the EBV DNA load,namely the EBV DNA<400 copies/ml group and the EBV DNA≥400copies/ml group.EBV DNA<400 copies/ml group and EBV DNA≥400copies/ml group 3 years OS,PFS,DMFS and LRFS were 99.2%vs.90.1%(P=0.001),96.7%vs.90.1%(P=0.028),98.4%vs.90.1%(P=0.005)and 98.4%vs100%(P>0.05).3.The EBV DNA load of NPC patients before treatment is negatively correlated with the ratio of CD19~+B cells(r=-0.138,P=0.040);and EBV DNA load with other circulating immune cell subsets,including peripheral blood innate immune cells(the ratio of CD56~+NK cells)and peripheral blood adaptive immune cells(CD3~+T lymphocytes,CD3~+CD4~+T lymphocytes,the ratio of CD3~+CD8~+T lymphocytes and the ratio of CD4~+/CD8~+),no significant correlation(P>0.05)4.Multivariate analysis showed that EBV DNA load was an independent prognostic factor for NPC patients with 3-year OS(P=0.024);CD19~+B cell ratio was an independent prognostic factor for NPC patients with 3-year PFS(P=0.039)、DMFS(P=0.036)and OS(P=0.015).5.The peripheral blood circulating immune cell subsets of NPC patients who used Thymus method and those who did not use thymosin were compared and analyzed before and after treatment.The CD3~+T cell ratio,CD3~+CD4~+T cell ratio,CD4~+/CD8~+ratio and CD56~+NK cell ratiothe ratio in the thymosin group increased compared with before treatment,and the proportion of CD8~+T cells was lower than before treatment(P<0.05);The ratio of CD19~+B cells,regardless of whether thymus method is used or not,is lower than before treatment(P<0.05);6.There was no significant difference in OS,PFS,DMFS,LRFS between NPC patients using Thymus Method and not using Thymus Method for 3 years(P>0.05).Conclusion:Before treatment,there is a negative correlation between the proportion of CD19~+B cells and plasma EBV DNA in peripheral blood.Both can be used as predictors prognostic indicators of NPC.Thymalfasincan improve the immune function status of NPC patients by activating the peripheral blood circulating immune cell subsets,and its influence on the prognosis of NPC patients remains to be further studied.