| 111 | 1 | 21 |
| 下载次数 | 被引频次 | 阅读次数 |
目的探究宫颈鳞癌(CSCC)患者外周血中人乳头状瘤病毒16型(HPV16)L1和L2多肽特异性细胞毒性T细胞(CTL)免疫反应水平及其与临床特征相关性,为其免疫治疗提供实验依据。方法选择2014年3月-2016年7月新疆医科大学附属肿瘤医院由病理明确诊断的宫颈鳞癌患者118例,采用酶联免疫斑点法(ELISPOT)检测患者外周血单个核细胞(PBMC)经合成的HPV16L1和L2抗原重叠肽刺后,分泌干扰素γ(IFN-γ)的CTL细胞的频率及强度,并分析其与临床特征之间的相关性。结果 (1)118例宫颈鳞癌患者外周血中HPV16L1和L2特异性CTL免疫应答阳性率分别为31.4%和16.9%;平均反应强度分别为36.3及30.3SFC/106PBMC。(2)HPV16L1和L2特异性抗原多肽反应频率在临床分期Ⅰ~Ⅱ期组均高于Ⅲ~Ⅳ期组(P=0.003,P=0.002);在HPV16阳性组均高于阴性组(P=0.002,P=0.015),余临床特征比较差异均无统计学意义。(3)HPV16L1特异性抗原多肽反应强度在组织学类型中,菜花型>空洞型>结节型>其他类型(P=0.019);HPV16L2特异性抗原多肽反应强度≤56岁组高于>56岁组(P=0.012),余临床特征比较差异均无统计学意义。结论宫颈鳞癌患者外周血中,HPV16L1和L2抗原肽可以诱导产生特异性CTL反应,并与HPV16感染、临床分期和组织学类型等临床特征有一定相关性,有可能成为宫颈鳞癌免疫治疗的潜在靶点。
Abstract：Objective To investigate the level of HPV16 L1 and L2 polypeptide-specific cytotoxic T cell(CTL)immune response in peripheral blood of patients with cervical squamous cell carcinoma(CSCC)and its correlation with clinical features for providingthe experimental basis for immunotherapy of CSCC.Methods 118 patients with CSCC diagnosed by pathology from March 2014 to July 2016 at the Affiliated Cancer Hospital of Xinjiang Medical University were enrolled.The frequency and intensity of CTL cells in peripheral blood mononuclear cells(PBMC)of patients with HPV16 L1 and L2 antigen overlapping peptides were detected by enzyme-linked immunospot assay(ELISPOT),and its relationship between CTL cells with clinical features and prognosis of patients was analyzed.Results(1)The positive rates of L1 and L2-specific CTL immune responses in peripheral blood of 118 patients with CSCC were 31.4% and16.9%,respectively;the mean response intensity was 36.3 and 30.3 SFC/106 PBMC,respectively.(2)The frequency of L1 and L2-specific antigen-specific peptides in the clinical stageⅠ-Ⅱ group was higher than that in theⅢ-Ⅳ group(P =0.003,P =0.002);The HPV16-positive group was higher than the negative group(P =0.002,P =0.015),there was no significant difference in the remaining clinical features.(3)Response magnitude of L1 specific antigen polypeptides in the histological type cauliflower>cavity type> nodule type> other types(P =0.019);L2 specific antigen peptide reaction magnitude in the≤56 years higher than >56 years old group(P =0.012),There was no statistically significant difference in the other clinical features.Conclusion HPV16 L1 and L2 antigen peptides can induce specific CTL response in peripheral blood of patients with squamous cell carcinoma of the cervix,and have certain correlation with clinical features such as HPV16 infection,clinical stage,histological type,etc.It may be a potential target for immunotherapy of cervical squamous cell carcinoma.
[1]CHEN W,ZHENG R,BAADE PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[2]SMALL W J R,BACON M A,BAJAJ A,et al.Cervical cancer:A global health crisis[J].Cancer,2017,123(13):2404-2412.
[3]ZHANG R,VELICER C,CHEN W,et al.Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grades 1or worse among 4215Chinese women in a population-based study[J].Cancer Epidemiol,2013,37(6):939-945.
[4]乔友林,赵宇倩.宫颈癌的流行病学现状和预防[J].中华妇幼临床医学杂志(电子版),2015,11(2):1-6.
[5]BARTOSIK M,DUNKOVA H,VOJTESEK B,et al.Electrochemical chip-based geomagnetic assay for detection of highrisk human papillomavirus DNA[J].Biosens Bioelectron,2016(83):300-305.
[6]BAKER T S,NEWCOMB W W,OLSON N H,et al.Structures of bovine and human papillomaviruses:analysis by cryoelectron microscopy and three-dimensional image reconstruction[J].Biophys J,1991,60(6):1445-1456.
[7]袁玉亮.基因重组HPV16L1蛋白的血清学实验在人乳头瘤病毒16感染诊断中的应用价值[J].中国妇幼保健,2016,31(16):3387-3389.
[8]ANATOLI M,MALYGUINE,SUSAN S,et al.ELISPOT assay for monitoring cytotoxic T lymphocytes(CTL)activity in cancer vaccine clinical trials[J].Cells,2012,1(2):111-126.
[9]WENTZENSEN N.Epidemiology,prevention and early detection of cervical cancer[J].Onkologe(Berl),2016,22(10):725-736.
[10]PALMA S,NOVELLI F,PADUA L,et al.Interaction between glutathione-S-transferase polymorphisms,smoking habit,and HPV infection in cervical cancer risk[J].J Cancer Res Clin Oncol,2010,136(7):1101-1109.
[11]范飞,柳欣林,李智海,等.人乳头瘤病毒衣壳蛋白结构生物学研究进展[J].中国生化药物杂志,2016,36(5):20-23,27.
[12]RICHARDS K F,BIENKOW M,DASGUPTA J,et al.Multiple heparansulfate binding site engagements are required for the infectious entry ofhuman papillomavirus type 16[J].J Virol,2013,87(21):11426-11437.
[13]BUCK C B,DAY P M,TRUS B L.The papillomavirus major capsid protein L1[J].Virology,2013,445(1):169-174.
[14]LETIAN T,TIANYU Z.Cellular receptor binding and entry of humanpapillomavirus[J].Virol J,2010(7):2.
[15]PINTO L A,EDWARDS J,CASTLE P E,et al.Cellular immune responses to human papillomavirus(HPV)-16L1in healthy volunteers immunized with recombinant HPV-16L1virus-like particles[J].J Infect Dis,2003,188(2):327-338.
[16]蒋蓉,李军强,杨鸣鸣,等.人乳头瘤病毒L2蛋白的病毒样颗粒疫苗研究[J].中国免疫学杂志,2016,32(3):366-371.
[17]HITZEROTH I,PASSMORE J,SHEPHARD E,et al.Immunogenicity of an HPV-16L2DNA vaccine[J].Vaccine,2009,27(46):6432-6434.
[18]CHIEW K L,CHONG S,DUGGAN K J,et al.Assessing guideline adherence and patient outcomes in cervical cancer[J].Asia Pac J Clin Oncol,2017,13(5):373-380.
[19]GUDLEVICIENE Z,KANOPIENE D,STUMBRYTE A,et al.Integration of human papillomavirus type 16in cervical cancer cells[J].Open Med(Wars),2015,10(1):1-7.
[20]DELIGEOROGLOU E,GIANNOULI A,ATHANASOPOULOS N,et al.HPV infection:immunological aspects and their utility in future therapy[J].Infect Dis Obstet Gynecol,2013,(2013):540850.
[21]JANETZKII S,RABIN R.Enzyme-linked immuno spot(ELISpot)for single-cell analysis[J].Methods Mol Biol,2015(1346):27-46.
[22]马苗苗,常雪梅,董涛,等.ELISPOT与Cultured ELISPOT检测宫颈癌HPV16抗原多肽特异性CTL反应分析[J].新疆医科大学学报,2017,40(7):862-865,870.
[23]黄莉,范佩文,刘凯,等.头颈部肿瘤外周血HPV特异性CTL免疫反应分析[J].新疆医科大学学报,2017,40(7):857-861.
基本信息:
中图分类号:R737.33
引用信息:
[1]范佩文,秦永辉,玛依努尔·阿里甫,等.宫颈鳞癌患者外周血中HPV16 L1和L2特异性CTL免疫反应相关性分析[J].新疆医科大学学报,2018,41(08):938-942.
基金信息:
国家自然科学基金(U1603282)
2018-08-15
2018-08-15