Objective:To explore the effect of clinical conventional fractionated dose radiation on the expression levels of immunogenic cell death (ICD) related proteins in patients with nasopharyngeal carcinoma (NPC).Methods:A total of 38 newly-treated NPC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from November 2020 to December 2021 were enrolled, all of whom received induction chemotherapy and concurrent chemoradiotherapy, and another 20 healthy volunteers were selected as controls for a prospective study. The contents of ICD related proteins, namely calreticulin (CRT), high mobility group box 1 protein (HMGB-1) and heat shock protein 70 (HSP70) and the proportion of dendritic cell (DC) in the peripheral blood of patients were detected before treatment, after induction chemotherapy and after concurrent chemoradiotherapy, respectively. The correlation between the above indicators, general clinical data and short-term efficacy was analyzed by statistical methods such as t-test and analysis of variance (ANOVA). Results:The levels of HSP70 and HMGB-1 in peripheral blood of NPC patients before treatment were higher than those of healthy controls (both P<0.05). After concurrent chemoradiotherapy, the content of CRT was significantly higher than that before treatment ( P<0.05), whereas the difference before and after induction chemotherapy and the difference before and after concurrent chemoradiotherapy were not significantly correlated with the short-term efficacy of NPC patients. HSP70 level was significantly decreased after concurrent chemoradiotherapy ( P<0.001). There were no significant differences in the content of HMGB-1 after induction chemotherapy and concurrent chemoradiotherapy (both P>0.05). Conclusion:NPC patients receiving TPF regimen (docetaxel+cisplatin+fluorouracil) for induction chemotherapy and sequential cisplatin concurrent chemotherapy may induce ICD in NPC cells, and CRT has potential value in reflecting the clinical efficacy of NPC.
Objective To explore the changes of lymphocytes and dendritic cells(DC)subsets in peripheral blood of patients with locally advanced nasopharyngeal carcinoma before and after induction chemotherapy and concurrent radiotherapy and chemotherapy,as well as their relationship with clinical prognosis.Methods Clinical data of patients with 134 patients with local advanced nasopharyngeal cancer at the Guizhou Medical University Affiliated Cancer Hospital of from 2016-12-05 to 2018-05-31 were retrospectively analyzed.All patients accept 2 to 3 cycles of Doxisca+Cisplatin+Fluoropromoline(TPF scheme)induced chemotherapy+platinum scheme combined with radiation chemotherapy.Before and after induc-tion chemotherapy and 1 week within concurrent radiation and chemotherapy,flow cytometry was used to detect lympho-cytes and DC subgroups in peripheral blood.The follow-up was once in every 3 months within 2 years after the treat-ment;once in every 6 months in 3 to 5 years.The survival was observed.The Friedman M test was used to compare lym-phocytes and DC subgroups in peripheral blood before treatment,after induction chemotherapy,and after concurrent che-moradiotherapy.ROC curves were used to determine the critical values of corresponding indicators.The Kaplan-Meier method and the COX regression model were used for survival analysis.Results The levels of CD3+[60.29(51.76,67.49)vs 63.85(58.63,70.10)],CD4+[32.31(25.97,38.26)vs 34.10(28.28,40.90)],CD8+[20.64(16.26,27.48)vs 23.32(18.37,29.10)],activated CD4+[1.36(0.90,2.61)vs 2.02(1.14,2.82)],activated CD8+[0.77(0.38,2.11)vs 1.90(0.78,4.00)],CD8+CD28+[12.08(9.16,15.01)vs 13.86(10.34,16.63)]and the myeloid dendritic cells[MDC;5.04(2.73,7.07)vs 6.06(4.26,9.28)]in peripheral blood increased after TPF induction chemotherapy(P<0.05).Af-ter concurrent radiotherapy and chemotherapy,the levels of CD3+[60.29(51.76,67.49)vs 57.60(47.39,66.50)],CD4+[32.31(25.97,38.26)vs 26.06(20.06,32.29)],CD8+CD28+[12.08(9.16,15.01)vs 10.09(6.74,13.15)],CD4+/CD8+[1.58(1.07,1.97)vs 1.22(0.82,1.71)]and CD4+CD25+[4.10(2.79,5.60)vs 3.15(1.49,5.37)]reduced(P<0.05).Kaplan Meier univariate analysis showed that the proportions of CD3+,CD4+,activated CD4+,CD8+CD28+,CD4+/CD8+,CD3-CD16+,plasmacytoid dendritic cells(pDC)and MDC in peripheral blood before treatment were correlated with patient survival prognosis(P<0.05).The prognostic analysis of the COX model found that high-lev-el CD4+(HR=0.39,95%CI:0.18-0.89,P=0.021)and PDC(HR=0.37,95%CI:0.15-0.90,P=0.030)were in-dependent influencing factors of overall survival for locally advanced nasopharyngeal cancer.Conclusions TPF-based in-duction chemotherapy may kill tumor cells,release tumor-related antigens,relieve the immunosuppressive state of locally advanced nasopharyngeal carcinoma,improve the tumor microenvironment and restore the body's immune function.After concurrent radiotherapy and chemotherapy,the body's immune function declines.CD4+and pDC in peripheral blood be-fore treatment may be independent influencing factors of OS in locally advanced nasopharyngeal carcinoma.
目的 探讨丝切蛋白1(Cofilin-1)、磷酸化丝切蛋白1(p-Cofilin-1)及树突状细胞(DCs)亚群在鼻咽癌组织中的表达及与预后的关系.方法 回顾性分析2011年1月至2015年12月97例鼻咽癌患者的临床资料,采用免疫组化法检测鼻咽癌组织中Cofilin-1、p-Cofilin-1及CD11c+DCs的表达情况.分析三者表达与鼻咽癌临床病理特征和预后的关系.结果 97例鼻咽癌患者中,Cofilin-1低表达率为26.8%(26/97),高表达率为73.2%(71/97);p-Cofilin-1低表达率为27.8%(27/97),高表达率为72.2%(70/97).CD11c低表达率为80.4%(78/97),高表达率为19.6%(19/97).M分期、临床分期、治疗后转移、治疗前骨转移和治疗后出现骨转移与Cofilin-1的表达有关(P<0.05);治疗后转移和治疗后出现骨转移与p-Cofilin-1的表达有关(P<0.05);CD11c表达与鼻咽癌临床病理参数均无关(P>0.05).Cofilin-1低表达组和高表达组1、3、5年生存率分别为84.6%、73.1%、73.1%和93.0%、61.7%、46.7%(P=0.094);低表达组和高表达组1、3、5年无远处转移生存率分别为100.0%、100.0%、100.0%和87.2%、73.3%、68.6%(P=0.002).p-Cofilin-1低表达组和高表达组1、3、5年生存率分别为85.2%、51.9%、40.4%和92.9%、72.7%、59.3%(P=0.075);低表达组和高表达组1、3、5年无远处转移生存率分别为83.5%、53.7%、53.7%和95.1%、89.9%、85.5%(P=0.001).CD11c低表达组和高表达组1、3、5年生存率分别为89.7%、61.3%、46.5%和94.7%、89.5%、89.5%(P=0.007);低表达组和高表达组1、3、5年无远处转移生存率分别为88.8%、80.2%、76.1%和100.0%、93.8%、87.1%(P=0.175).结论 Cofilin-1表达水平越高,肿瘤转移风险越高,无远处转移生存时间越短;p-Cofilin-1表达水平越高,肿瘤发生转移的风险越低,无远处转移生存时间越长;CD11c表达水平越高,总生存时间越长.Cofilin-1、p-Cofilin-1、CD11有望成为鼻咽癌靶向治疗和预后预测的标志物.
目的 >90%头颈部肿瘤病理类型以鳞癌为主,需要稳定且有效的生物学指标来预测患者预后、指导治疗.本研究探讨肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TILs)对头颈部鳞癌(head and neck squamous cell,HNSCC)的预后价值.方法 以"头颈鳞癌、肿瘤微环境、TILs、免疫细胞和预后价值"为关键词,应用PubMed及CNKI期刊全文数据库主要检索2015-01-2018-12的相关文献及注册临床研究.纳入标准:(1)HNSCC;(2)TILs;(3)TILs与预后的相关临床研究.共纳入30篇文献进行分析.结果 肿瘤微环境是独特、复杂的环境,存在大量的淋巴细胞浸润,主要是T淋巴细胞,其亚型包括了CD3+、CD4+和CD8+T淋巴细胞等.肿瘤浸润淋巴细胞TILs在HNSCC中具有显著的预后价值,与较好的总生存率(overall survival,OS)、无进展生存期(progression-free survival,PFS)和无远处转移生存率(dis-tant metastasis-free survival,DMFS)等是显著相关的.同时TILs每个亚群的作用机制不尽相同,导致了TILs在肿瘤微环境中的作用尚不十分明确.除了与淋巴细胞亚群有关外,人类乳头瘤病毒(Human papillomavirus,HPV)、人类疱疹病毒(Epstein-Barr virus,EBV)、生物学因素和评估方法都可作为影响TILs评估HNSCC预后价值的相关因素.结论 TILs在HNSCC中具有较高的预后价值,但肿瘤微环境仍有很多机制不明.