| Nasopharyngeal carcinoma(NPC)is a malignant tumor of the head and neck derived from the nasopharyngeal epithelium.It is mainly distributed in North and East Africa,South China,and East and Southeast Asia.According to statistics,there are 133354 new cases of nasopharyngeal carcinoma and 80008 deaths worldwide in 2020.In recent years,major progress has been made in the diagnosis and treatment of nasopharyngeal carcinoma patients,including screening technology,intensity-modulated radiotherapy and targeted therapy.The total 5-year survival rate of early nasopharyngeal carcinoma is more than 80%,and the total 5-year survival rate of intermediate and advanced nasopharyngeal carcinoma is between 50% and 60%.Because the early manifestations of nasopharyngeal carcinoma are very hidden,leading to more than 60% of patients being diagnosed in the late stage.About 15%～30% of the patients will eventually relapse.Once the patients have recurrence or metastasis,their survival prognosis is very poor.Early detection and early treatment are effective ways to improve the diagnosis and treatment of NPC.Due to nonspecific clinical manifestations and lack of biomarkers for early detection of metastases in patients,it ultimately leads to delayed treatment and poor prognosis.Therefore,we expect to develop a highly specific and sensitive prognostic model for the prognosis of nasopharyngeal carcinoma.ObjectiveThe purpose of our study was to investigate the relationship between the heterogeneity of the abundance of immune cell infiltration in TME and the clinicopathologic features of patients with nasopharyngeal carcinoma in the real world,so as to establish an effective immune evaluation system.To analyze the relationship among immune subgroups and clinical case characteristics and prognosis of nasopharyngeal carcinoma,and establish prognosis prediction model of nasopharyngeal carcinoma.MethodsIn this study,a single center retrospective method was used.A total of 151 patients with nasopharyngeal carcinoma who were hospitalized and treated in the Oncology Department of the First People’s Hospital of Jingzhou from January 2012 to December2015 were enrolled.The patients were randomly divided into training group and validation group with a ratio of 7:3.The training set data were used to screen prognostic variables and construct a prognostic model,and the validation set data were used to test and evaluate the prognostic model.The patients immunscore(IS)of CD4,CD8,CD20,CD163 and CD73 was calculated by immunohistochemical staining.The Kaplan-Meier method was used to analyze the relationship among different immune cell subtypes and OS and PFS in patients with NPC,and log-rank test was used to compare the differences between groups.Cox proportional hazards model was used for univariate and multivariate analysis to determine the independent risk factors for PFS or OS,and the HR and 95%confidence interval were calculated.Finally,nomograms for predicting 3-year or 5-year OS were developed based on independent variables.The consistency index(C-index)was used to evaluate the accuracy of the nomogram,and the calibration chart was used to evaluate its prognosis ability.Results1.The spatial distribution of immune cells in TME of NPC was significantly different.The average IS of CD4 in(Center Tumor,CT/ Invasive Margin,IM)region was 0.613± 1.047/2.434 ± 1.789;The average IS of CD8 in(CT/IM)region was 3.566 ±2.878/4.189±2.322.The average IS of CD20 in(CT/IM)was 1.886±1.811/3.603±2.562.The average IS of CD73 on(CT/IM)was 2.311±1.551/7.113±2.020.The average IS of CD163 in(CT/IM)was 2.179±2.119/4.990±2.561.2.The mean overall survival time of low CD4(IM)score group VS high CD4(IM)score group was 73.7 months VS 91.1months,P<0.05,HR=2.222,95%CI 1.062～4.649;The mean overall survival time of low CD4(CT)score group VS high CD4(CT)score group was 73.7 months VS 91.5 months,P<0.05,HR=2.216,95%CI 1.107～4.445.3.The mean overall survival time of CD8(IM)low score group VS high score group was 71.0 months VS 90.7 months,P< 0.05,HR=2.417,95%CI 1.237～4.725.4.The mean overall survival time of CD73(IM)high score group VS CD73(IM)low score group was 69.9 VS 88.4 months,P<0.05,HR=2.382,95%CI 1.265～4.487.The mean progression-free survival time of CD73(IM)high score group VS low score group was 73.9 months VS 92.3 months,P<0.05,HR=2.286,95%CI 1.087～4.810.5.No significant relationship was found between survival and tumor infiltration by CD20+B cells,or CD163+ macrophages.6.The mean overall survival time of low IS group VS high IS group was 68.4 months VS 93.6 months,P<0.05,HR=3.087,95%CI 1.548-6.155.The average progression-free survival time was 71.4 months VS 96.1 months in the low IS group VS the high IS group,P<0.05,HR=4.478,95%CI 1.823-10.999.7.The mean overall survival time of clinical stage Ⅳ VSⅠ～Ⅲ was 65.1 months VS 94.4 months,P<0.05,HR=3.645,95%CI 1.788-7.433.The mean progression-free survival time of clinical stage Ⅳ VSⅠ～Ⅲ was 72.1 months VS 92.7 months,P<0.05,HR=2.271,95%CI 1.061-4.864.Conclusion1.The infiltration of immune cell subtypes,including CD4+T cells,CD8+T cells,CD20+B cells and M2(CD163+)macrophages,was spatially heterogeneous in the NPC microenvironment.2.CD4 overexpression in the(IM/CT)region was associated with better prognosis in NPC patients.CD8 overexpression in IM region is associated with better prognosis in NPC patients3.There are spatial and individual differences in the expression of CD73 in the TME of nasopharyngeal carcinoma,and the overexpression of CD73 in the TME is closely related to the poor prognosis of patients with nasopharyngeal carcinoma.4.There was no significant correlation between the prognosis of NPC and CD20 or CD163.5.Total IS is not only an independent prognostic factor for OS,but also for PFS in NPC patients. |
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