白细胞介素-35对肝细胞癌患者CD4+CD25+CD127dim/-调节性T细胞的调控作用

目的 观察肝细胞肝癌(HCC)患者外周血白细胞介素-35(IL-35)水平和CD4⁺CD25⁺CD127^dim/-调节性T细胞(Treg)比例,评估IL-35对Treg数量和功能的影响。方法 共有51例HCC患者和25例对照者,分离外周血单个核细胞(PBMC)和血浆,实时定量PCR法检测PBMC中IL-35亚基mRNA相对表达量,酶联免疫吸附试验(ELISA)法检测外周血IL-35水平,流式细胞术检测PBMC中CD4⁺CD25⁺CD127^dim/-Treg比例。使用重组人IL-35(1 ng/ml)刺激HCC组PBMC 24 h,观察Treg比例和EBI3、IL-12p35 mRNA相对表达量的变化。分选17例HCC患者的Treg,经重组人IL-35刺激后与自体PBMC共培养48 h,通过检测细胞增殖和细胞因子表达评估IL-35对Treg功能的影响。组间比较采用t检验或配对t检验。结果 HCC组血浆IL-35水平显著高于对照组[(1024±218.0)pg...     

硼替佐米联合地塞米松、来那度胺化疗方案治疗多发性骨髓瘤的疗效和安全性评价

目的 探讨硼替佐米联合地塞米松、来那度胺化疗方案治疗多发性骨髓瘤的疗效及安全性。方法 将多发性骨髓瘤患者96例按随机数字表法分为观察组和对照组。对照组采用硼替佐米联合环磷酰胺、地塞米松化疗方案，观察组采用硼替佐米联合地塞米松、来那度胺化疗方案，均连续给予3个疗程的治疗(28 d为1个疗程)。将2组患者的各项指标进行统一的对比分析。结果 治疗后观察组患者的临床总有效率(93.75%)高于对照组(79.17%);治疗后2组患者的血清白细胞介素(IL)-6、IL-17、C反应蛋白(CRP)、M蛋白、β2微球蛋白水平、骨髓瘤细胞比例、外周血CD3⁺CD8⁺水平与治疗前比较均降低，观察组较对照组均处于较低水平；治疗后2组患者外周血CD3⁺CD4⁺、CD3⁺CD4⁺/CD3⁺CD8⁺、Treg、血清血红蛋白(Hb)水平与治疗前比较均升高，观察组较对照组均处于较高水平，有显著性差异(P均<0.05);治疗期间2组不良反应...     

CD+T细胞及Treg细胞表面PD-1水平与肺癌患者术后预后的关系

目的 探讨CD⁺T细胞及调节性T(Treg)细胞表面程序性死亡受体1(PD-1)水平与肺癌患者术后预后的关系。方法 选取行肺癌根治术的肺癌患者126例,统计术后2年内预后不良发生率,并根据其预后情况将其分为良好组和不良组,单因素分析肺癌患者术后预后不良的影响因素,Logistic回归分析肺癌患者术后预后不良的影响因素,受试者工作特征曲线(ROC)分析CD⁺T细胞及Treg PD-1水平对肺癌患者术后预后的预测价值。结果 两组肿瘤淋巴结转移(TNM)分期、CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺及Treg PD-1水平比较,均有显著差异(P<0.05);Logistic回归分析显示,CD3⁺、CD3⁺CD4⁺是肺癌患者术后预后不良的独立保护因素,CD3⁺CD8⁺、Treg PD-1是肺癌患者术后预后不良的独立危险因素(...     

调节性T细胞联合血清外泌体ZFPL1在非小细胞肺癌诊断中的临床意义

目的 探讨调节性T细胞(Treg)联合血清外泌体ZFPL1在非小细胞肺癌诊断中的价值。方法 收集2022年1月至2022年10月收治的非小细胞肺癌患者67例为观察组,选择同期健康体检者61例为对照组。采用流式细胞仪测定Treg细胞标志物CD3⁺CD8⁺和CD4⁺Foxp3⁺水平;采用实时荧光PCR(qPCR)测定血清外泌体ZFPL1水平,分析Treg及血清外泌体ZFPL1表达水平与临床病理特征的关系;绘制受试者特征工作曲线(ROC)评价Treg联合血清外泌体ZFPL1诊断非小细胞肺癌的效能。结果 观察组Treg细胞标志物CD3⁺CD8⁺水平为0.48±0.11,低于对照组的0.59±0.16(P<0.05);观察组血清外泌体ZFPL1水平和Treg细胞标志物CD4⁺Foxp3⁺水平分别为3.62(1.44,7.62)和0.76±0.06,高于对照组的0.91(0.17,3.43)和0.67±0.19,差异均...     

小鼠衰老所致“正虚”过程中免疫功能衰退表征的特点

目的：基于小鼠渐进衰老模型探讨衰老所致“正虚”的免疫功能衰退表征的特点。方法：使用不同月龄(2、6、15月龄)C57BL/6小鼠,通过流式细胞术检测并比较小鼠外周血和脾组织中T细胞、髓源性抑制细胞(MDSC)及其亚群的丰度变化。结果：外周血中T细胞亚群表型为CD3⁺CD4⁺CD44-CD62L⁺的幼稚CD4⁺T细胞(2 vs 6月龄,P=0.137;2 vs 15月龄,P=0.004;6 vs15月龄,P=0.105)和表型为CD3⁺CD8⁺CD44-CD62L⁺的幼稚CD8⁺T细胞(2 vs 6月龄,P=0.179;2 vs 15月龄,P=0.001;6 vs15月龄,P=0.015)出现与衰老有关的细胞比例降低,差异具有统计学意义。表型为CD3⁺CD4⁺CD44⁺CD62L⁺的中央记忆CD8⁺T细胞出...     

过继性免疫治疗对非小细胞肺癌患者外周血T细胞亚群的影响

目的 研究细胞因子诱导的杀伤（cytokine-induced killer,CIK）细胞治疗对非小细胞肺癌（non-small cell lung cancer,NSCLC）患者外周血T细胞亚群及一般情况的影响。方法 采集非小细胞肺癌患者外周血,常规方法体外扩增CIK细胞,分三次回输患者体内,流式细胞仪检测非小细胞肺癌患者治疗前与治疗3次后T细胞亚群的变化,分析其与健康对照组相比外周血T细胞亚群的差异,并观察CIK细胞治疗前后患者一般情况变化。结果 与对照组相比,NSCLC患者外周血中CD3⁺ T 细胞比例、CD3⁺CD4⁺T细胞比例、CD4⁺/CD8⁺ 比值显著下降（P<0.05）,CD3⁺CD8⁺ T细胞比例显著升高（P<0.05）。CIK细胞治疗后与治疗前,CD3⁺ T 细胞比例、CD3⁺CD4⁺ T细胞比例、CD4⁺/CD8⁺ T细胞比值显著升高（P<0.05）,CD3⁺CD8⁺ T细胞比例显著降低（P<0.05）。CIK细胞治疗后与对照组相比,CD3⁺ T 细胞比例、CD4⁺/CD8⁺T细胞比值显著下降（P<0.05）。CD3⁺CD4⁺ T细胞比例、CD3⁺CD8⁺ T细胞比例升高,但差异无统计学意义（P>0.05）。CIK细胞治疗前Tregs较对照组显著升高（P<0.05）。CIK细胞治疗后与治疗前相比,Tregs比例显著下降（P<0.05）。结论 CIK细胞输注治疗可以增强NSCLC患者的免疫功能,并改善患者的一般情况,提高生活质量,且未见明显不良反应。     

儿童急性B淋巴细胞白血病缓解期外周血MDSCs的变化及意义

目的:观察儿童急性B淋巴细胞白血病(B-ALL)缓解期患者外周血髓系来源的抑制性细胞(MDSCs)的变化,并探讨其原因及可能的意义。方法:分别抽取22例儿童B-ALL行长春新碱、柔红霉素、左旋门冬酰胺酶和强的松(VDLP)方案化疗后缓解期患者和20例健康体检儿童的外周血,流式细胞术检测和分析CD33⁺HLA-DR^-/CD33⁺细胞比例、以及CD14⁺CD33⁺HLA-DR^-和CD15⁺CD33⁺HLA-DR^-两群MDSCs细胞比例的变化,统计分析B-ALL患者和健康对照组之间MDSCs的差异。结果:儿童B-ALL缓解期患者外周血CD33⁺HLA-DR^-MDSCs所占CD33⁺细胞的比例较健康对照组明显降低(P=0.001);单核细胞来源的CD14⁺CD33⁺HLA-DRMDSCs的比例较健康对照组显著降低(P<0.01);粒细胞来源的CD15⁺CD33⁺HLA-DR^- MDSCs比例亦较健康对照组明显降低(P=0.004)。结论:儿童B-ALL患者行VDLP方案化疗后完全缓解期患者外周血MDSCs的比例明显下降,其低水平的MDSCs可能与化疗后机体免疫系统尚未完全正常建立相关。     

结直肠癌肿瘤微环境中调节性T细胞CD39、CD73亚群及二者双阳性亚群的临床意义

目的 观察结直肠癌肿瘤组织微环境中浸润的调节性T细胞的临床意义,并探究其CD39、CD73及CD39,CD73双阳性亚群与肿瘤微环境中其他淋巴细胞及临床病理参数之间的关系。方法 收集24例结直肠癌患者根治术后组织标本,剪碎并分离培养组织内肿瘤浸润淋巴细胞(Tumor infiltrating lymphocyte,TIL),以流式细胞术观察调节性T细胞CD39⁺、CD73⁺及CD39⁺CD73⁺亚群与患者临床病理参数之间的关联。结果 结直肠癌肿瘤组织微环境中浸润的调节性T细胞CD73⁺亚群,CD39⁺CD73⁺亚群与淋巴结转移及分化程度不良具有相关性,并且其机制与肿瘤相关性炎症密切相关。结论 相比Treg中的其他亚群,CD39⁺CD73⁺阳性的结直肠肿瘤浸润Treg具有更为独特的生物学活性,本研究为预测结直肠癌预后提供了新思路与理论依据。     

高强度聚焦超声对前列腺癌小鼠的疗效及T细胞亚群的影响

目的探讨高强度聚焦超声（high intensity focused ultrasound, HIFU）对前列腺癌荷瘤小鼠的疗效及T细胞亚群的影响。方法RM-1细胞接种于C57BL6小鼠建立小鼠前列腺癌皮下移植瘤模型,随机分为肿瘤对照组、HIFU组、放疗组和HIFU联合放疗组。观察治疗后各组的肿瘤生长曲线,计算肿瘤体积倍增时间（DT）。2周后,通过流式细胞仪检测正常小鼠和荷瘤小鼠外周血CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺ 细胞占白细胞总数的百分比。结果与肿瘤对照组相比,HIFU组、放疗组肿瘤生长延缓,DT显著延长。HIFU组小鼠的CD3⁺(%)、CD4⁺(%)显著高于肿瘤对照组,而放疗组与肿瘤对照组差异无统计学意义。HIFU联合放疗组的DT较HIFU组显著延长,小鼠的CD3⁺(%)、CD4⁺(%)显著高于HIFU组,且CD4⁺(%)显著高于正常小鼠。结论HIFU治疗前列腺癌不仅能局部抑制肿瘤生长,而且能通过对T细胞亚群的影响提高机体的细胞免疫水平。HIFU联合放疗能进一步提高疗效。     

脑胶质瘤术后外周血T淋巴细胞水平变化及其与颅内感染的关系

目的探讨脑胶质瘤术后外周血T淋巴细胞水平变化及其与颅内感染的关系。方法选取92例行手术治疗的脑胶质瘤患者,根据胶质瘤级别分为低级组(n=42)、高级组(n=50),比较2组手术前后T淋巴细胞水平变化;根据术后是否出现颅内感染,分为感染组(n=15),未感染组(n=77),分析T淋巴细胞水平与颅内感染的关系。结果手术前,高级组外周血CD3⁺、CD4⁺、CD4⁺/CD8⁺均显著低于低级组,CD8⁺显著高于低级组;术后7 d,高级组外周血CD3⁺、CD4⁺、CD4⁺/CD8⁺均显著低于低级组,CD8⁺显著高于低级组(P<0.05)。92例行手术治疗的脑胶质瘤患者术后颅内感染率为16.30%(15/92),其中高级别胶质瘤患者11例、低级别胶质瘤患者4例。手术前,感染组和非感染组外周血CD3⁺、CD4⁺、CD4⁺/CD8⁺、CD8⁺比较未见差异(P>0.05)。术后7 d,感染组外周血CD3⁺、CD4⁺均显著低于非感染组,CD8⁺显著高于非感染组(P<0.05)。ROC曲线分析显示,外周血CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺四者联合预测脑胶质瘤患者术后颅内感染的AUC为0.892,高于单独检测的0.814、0.756、0.699、0.748。结论脑胶质瘤患者经手术治疗可显著改善外周血T淋巴细胞水平,低级别胶质瘤患者免疫抑制改善程度优于高级别胶质瘤患者。外周血CD3⁺、CD4⁺、CD4⁺/CD8⁺、CD8⁺四者联合可用于胶质瘤患者术后颅内感染的评估。     

Proportion of CD4+CD25+ regulatory T cell is increased in the patients with ovarian carcinoma

Objective: To study the frequency of the CD4⁺CD25⁺ regulatory T cells (Tregs) in the patients with ovarian carcinoma and its possible mechanism. Methods: The percentages of CD4⁺CD25⁺ Tregs in the peripheral blood lymphocytes (PBLs), tumor infiltrating lymphocytes (TILs) and tumor associated lymphocytes (TALs) from 13 patients with ovarian carcinoma and in the PBLs from 14 healthy women were determined by flow cytometry. The expression of CD69 on CD4⁺PBLs from the patients was detected. PBLs from healthy women were cultured in complete RPMI 1640 containing the supernatant from SKOV3 cell line with or without PHA (phytohemagglutinin) stimulation for 72 hours, then the percentage of CD4⁺CD25⁺ T cells was detected. Results: CD4⁺CD25⁺ Tregs in the PBLs from patients with ovarian carcinoma were significantly increased compared with those from the control. The percentage of CD4⁺CD25⁺ Tregs in TILs was higher than that in PBLs and TALs from the patients, but not significantly. The expression of CD69 on CD4⁺PBLs from the patients was negative. The percentages of CD4⁺CD25⁺ T cells in PBLs cultured with SKOV3 supernatant elevated significantly compared with those without supernatant whether PHA was added or not (P = 0.001 and 0.001, respectively). Conclusion: There is an increasing of the proportion of CD4⁺CD25⁺ Tregs in PBLs, TILs and TALs of the patients with ovarian carcinoma, which probably results from up-regulation of soluble factor secreted by ovarian carcinoma cells.     

肝细胞癌组织ICOS+T细胞的多重免疫组织化学检测及其预后价值研究

背景与目的：诱导共刺激分子（inducible costimulator,ICOS）属于B7-CD28免疫球蛋白超家族成员,表达于活化T细胞表面,在T细胞的激活和免疫应答中发挥重要作用;但目前对于ICOS及ICOS+ T细胞在肝细胞癌（hepatocellular carcinoma,HCC）肿瘤组织中的表达及其意义尚不清楚。该研究旨在测定ICOS、ICOS⁺ T细胞在HCC患者肿瘤组织中的表达情况并探讨其预后价值。方法：应用组织芯片（tissue microarrays,TMAs）和多重免疫组织化学技术（multiplex immunohistochemistry,mIHC）检测2006—2007年在复旦大学附属中山医院接受手术治疗的358例原发性HCC患者肿瘤组织和癌旁组织中ICOS⁺细胞、ICOS⁺CD4⁺及ICOS⁺CD8⁺ T细胞的浸润密度和ICOS⁺细胞占CD4⁺、CD8⁺ T细胞的百分比。应用Kaplan-Meier法和多因素COX回归模型分析上述指标对患者预后的影响。结果：与癌旁组织相比,ICOS⁺细胞和ICOS⁺CD4⁺ T细胞在肿瘤组织中浸润数量显著增加（P<0.000 1和P=0.009 1）,而ICOS⁺CD8⁺ T细胞则呈相反的降低趋势（P=0.033）;在肿瘤中,ICOS⁺CD4⁺ T细胞的浸润程度显著高于ICOS⁺CD8⁺ T细胞。此外,ICOS⁺CD4⁺和ICOS⁺CD8⁺ T细胞占各自T细胞亚群的百分比在肿瘤组织中均显著增加（P均<0.000 1）。预后分析发现,肿瘤组织中ICOS⁺细胞、ICOS⁺CD4⁺及ICOS⁺CD8⁺ T细胞浸润高的患者总生存期（overall survival,OS）更长,多因素分析证实上述指标是HCC的独立预后良好因素。结论：ICOS在HCC患者的肿瘤组织中高表达,且ICOS⁺细胞、ICOS⁺CD4⁺及ICOS⁺CD8⁺ T细胞是OS的独立预后良好因素,提示上述指标可作为新的HCC预后免疫标志物。     

乙型肝炎性肝癌和酒精相关性肝癌患者外周血中T细胞亚群表达差异和价值

目的:分析乙型肝炎性肝癌（HBV-HCC）和酒精相关性肝癌（ALC-HCC）患者外周血中T 细胞亚群表达差异和价值。方法:将2016年07月至2018年10月期间于本院接受诊治的65例乙型肝炎性肝癌患者作为HBV-HCC组,另选择同期于本院接受诊治的58例酒精相关性肝癌患者作为ALC-HCC组。经全自动生化分析仪及流式细胞仪对两组患者的T细胞亚群指标表达情况进行检测,并对比分析两组患者的肝功能Child-Pugh分级。结果:两组患者的肝功能Child-Pugh分级对比,差异无统计学意义（P＞0.05）;HBV-HCC组患者外周血中CD3+、CD8+、CD4+CD45RA+值高于ALC-HCC组,但外周血中CD4+、CD4+/CD8+、CD4+CD25+、CD8+CD28+值低于ALC-HCC组,差异有统计学意义（P＜0.05）;单因素分析发现,患者年龄、BMI、手术类型、临床分期、原发病灶大小、血管浸润及生存时间中位数与患者预后存在相关性,差异有统计学意义（P＜0.05）;多因素Logistic回归分析发现,患者年龄≥60岁、BMI＞24 kg/m2、开腹手术、临床分期、原发病灶＞3.6 cm、血管浸润及生存时间中位数＜72个月是影响患者生存质量的独立因素,差异有统计学意义（P＜0.05）。结论:乙型肝炎性肝癌和酒精相关性肝癌患者外周血中T 细胞亚群表达具有明显差异,能视作临床评判肝癌患者病情演变及疗效、预后的重要指标。     

免疫磁珠分选的口腔鳞状细胞癌干细胞诱导分化及成瘤活性研究

目的 探讨口腔鳞状细胞癌干细胞的诱导分化及成瘤活性。方法 采用免疫磁珠分选法从6例原代培养的口腔鳞状细胞癌细胞中分选出CD133⁺、CD44⁺细胞，以流式细胞术检测其纯度及细胞周期，并绘制CD133⁺细胞生长曲线。将分选出的细胞经诱导向成骨肪细胞及成脂肪细胞分化，将原代鳞癌细胞、分选所得的CD44⁺细胞及CD133⁺细胞进行体内成瘤实验。 结果 经免疫磁珠分选法成功获得CD44⁺细胞、CD133⁺细胞，其纯度经检测均在94%以上，且主要处于G0/G1期。CD133⁺细胞在接种后第2天进入对数期，细胞倍增时间为3.22 d。经诱导后CD44⁺、CD133⁺细胞成功分化为成骨细胞及成脂肪细胞。皮下注射后第3天可触及新生肿物，在3种细胞成瘤实验中CD133⁺细胞组瘤体体积最大，HE染色显示符合低分化口腔鳞状细胞癌病理表现。结论 免疫磁珠分选法可高效获得高纯度的口腔鳞状细胞癌干细胞。CD44⁺、CD133⁺细胞均具有较强的多向分化能力，CD133⁺细胞成瘤性较强。     

T-Cell Membrane CD45RA (2H4) and CD45RO (UCHL1) Determinants: I, Diverse Patterns of Expression in Mature (Post-Thymic) T-Cell Proliferations

By simultaneous two- and three-colour flow cytometry, this study analysed the expression of membrane CD45RA (2H4) and CD45RO (UCHL1) determinants by normal thymocytes (n = 5) and peripheral blood lymphocyte subpopulations (CD4⁺, n = 21; CD8⁺, n = 12; CD8^dim+, n = 12) and compared these patterns with those of T-cells from representative CD4⁺CD8^- (n = 8), CD4⁺CD8⁺ (n = 2), CD4^-CD8⁺ (n = 10) and CD4^-CD8^- (n = 1) proliferations. These comprised cases of prolymphocytic leukaemia (T-PLL, n = 5), adult T-cell leukaemia-lymphoma (ATLL, n = 2), Sezary Syndrome (SS, n = 4), chronic lymphocytic leukaemia (T-CLL, n = 4), and lymphoproliferative disease of granular lymphocytes (LDGL, n = 5). Normal thymocyte fractions, of which a mean of 85% cells co-expressed membrane CD4 and CD8, were predominantly (mean 89%) 2H4^-UCHL1⁺ with the remaining cells consisting of 2H4^intUCHL1⁺ and 2H4⁺UCHL1^- components. Further analysis showed that virtually all CDla⁺ thymocytes were UCHL1⁺ whereas the CD1a^- fraction comprised similar proportions of both UCHL1^- and UCHL1⁺ subpopulations. Similarly, normal blood CD4⁺, CD8⁺ and CD8^dim+ lymphocytes showed reciprocal CD45RA/CD45RO expression and could be phenotypically grouped into 2H4⁺UCHL1^- 2H4^intUCHL1⁺ and 2H4^-UCHL1⁺ subpopulations. Mean proportions of 48% and 68%, for CD4⁺ and CD8⁺ lymphocytes respectively, showed a composite 2H4⁺UCHL1^- phenotype, whereas the percentage of NK-associated CD8^dim+ cells with this phenotypic pattern was considerably higher (mean, 85%). Normal lymphocyte subpopulations lacking both determinants (2H4^-UCHL1^-) were only rarely noted. Comparing normal patterns of CD45RA/CD45RO expression with those of the T-cell proliferations revealed diverse and abnormal patterns of staining for 3/6 of the CD4⁺CD8^- SS and ATLL, and for 5/5 of the T-PLL (CD4⁺CD8^-, n = 2; CD4⁺CD8⁺, n = 2; and CD4^-CD8⁺, n = 1) cases studied. In contrast, the nine cases of CD4^-CD8⁺ T-CLL and LDGL all showed CD45RA/CD45RO staining patterns similar to that of normal CD8⁺/CD8^dim+ blood lymphocytes (i.e. a predominance of 2H4⁺UCHL1^- cells). Although the variant CD45RA/CD45RO pattern types of the CD4⁺ proliferations did not appear to be related to either the diagnostic category or other phenotypic characteristics, the high proportion of abnormal patterns within this case group suggests that recognition of these abnormalities may be potentially relevant to the differentiation of benign and malignant CD4⁺ proliferations and, in addition, may be of aetiological importance with respect to the diverse acquired defects in immunity commonly seen in patients with such disorders.     

B细胞易位基因2在食管鳞癌组织中的表达及临床意义

目的:探讨B细胞易位基因2（BTG2）在食管鳞状细胞癌（ESCC）组织中的表达及临床意义。方法:分析癌症基因组图谱（TCGA）数据库中BTG2 mRNA在ESCC组织及癌旁组织中的表达,受试者工作特征（ROC）曲线分析BTG2 mRNA表达量在预测ESCC患者疾病状态和放疗敏感性中的诊断价值;免疫组织化学检测我院184例ESCC患者癌组织标本BTG2蛋白表达,其中包括55例行根治性放疗术的ESCC患者,50例正常黏膜组织作为对照。分析BTG2蛋白表达情况与ESCC临床特征的关系。结果:与对照组比较,BTG2 mRNA在ESCC组织中表达下降（5.08±1.06 vs 5.91±1.29,t=2.387,P=0.019）,与放疗敏感组患者比较,BTG2 mRNA在放疗抵抗的ESCC患者癌组织中表达下降（3.82±0.97 vs 5.44±0.73,t=4.935,P＜0.001）,ROC结果显示BTG2 mRNA在鉴别放疗敏感与放疗抵抗患者时特异性为95.65%,敏感性为75%（AUC=0.902,P＜0.001）;免疫组织化学结果显示ESCC组织中BTG2阳性表达（103/184）低于正常黏膜组织（42/50）,差异有统计学意义（χ2=13.10,P＜0.001）;BTG2表达在放疗敏感和放疗抵抗组织中的阳性表达率分别为57.9%（22/38）和23.5%（4/17）,差异有统计学意义（χ2=5.565,P=0.018）;ESCC患者BTG2蛋白表达差异在不同性别、年龄、T分期及M分期中无统计学差异（P＞0.05）,与N分期（χ2=4.134,P=0.042）及临床分期（χ2=5.303,P=0.021）相关;单因素分析结果显示,肿瘤分级（HR=0.500,95%CI:0.317～0.790,P=0.003）、N分期（HR=0.275,95%CI:0.157～0.479,P=0.000）、M分期（HR=0.317,95%CI:0.151～0.665,P=0.002）、临床分期（HR=0.269,95%CI:0.167～0.434,P=0.000）及BTG2表达（HR=1.956,95%CI:1.242～3.079,P=0.003）与ESCC患者总生存（OS）有关;多因素分析结果显示,肿瘤分级（HR=0.613,95%CI:0.381～0.987,P=0.044）、N分期（HR=0.507,95%CI:0.259～0.991,P=0.047）、临床分期（HR=0.504,95%CI:0.278～0.916,P=0.025）及BTG2表达（HR=1.608,95%CI:1.011～2.558,P=0.045）影响ESCC患者的OS。结论:BTG2具有作为预测ESCC进展及放疗敏感性生物标记物的潜在价值,并且是影响ESCC患者总生存率的独立预后因素。     

结直肠癌及腺瘤患者CD4+、CD8+和CD28+T淋巴细胞的亚群变化及临床意义

背景与目的：结直肠癌（colorectal cancer,CRC）严重影响患者生存。探讨肿瘤微环境（tumor microenvironment,TME）T细胞亚群在CRC和腺瘤中的表达及意义。方法：用免疫组织化学法和流式细胞术对51例健康人（对照组）、46例结直肠腺瘤（腺瘤组）、100例CRC（癌症组）和15例CRC术后（癌术后组）患者进行T细胞亚群检测。结果：① 对照组、腺瘤组及癌症组3组中CD4⁺T细胞的阳性率分别是90.00%、43.75%及32.65%,CD8⁺T淋巴细胞的阳性率分别是30.00%、56.25%及75.51%,CD28⁺T淋巴细胞的阳性率分别是42.86%、30.00%及20.00%。② 对照组、腺瘤组及癌症组3组中CD4⁺、CD4⁺/CD8⁺、CD28⁺、CD8⁺CD28⁺和CD8^－CD28⁺逐渐降低,CD8⁺、CD8⁺CD28^－逐渐增加（P＜0.05）;癌术前术后T细胞亚群差异有统计学意义（P＜0.05）。结论：① CRC微环境T细胞亚群中CD4⁺、CD4⁺/CD8⁺、CD28⁺、CD8⁺CD28⁺和CD8^－CD28⁺呈递减趋势,CD8⁺、CD8⁺CD28^－呈递增趋势,且在癌前病变腺瘤中已逐步出现上述趋势变化。② CRC患者行肿瘤切除术后,其T细胞亚群有所恢复,故在一定程度上,CRC中T细胞亚群的变化可以早期预测结直肠疾病的发展。     

Adult T-cell leukemia/lymphoma cells from blood and skin tumors express cytotoxic T lymphocyte-associated antigen-4 and Foxp3 but lack suppressor activity toward autologous CD8+ T cells

Adult T cell leukemia/lymphoma (ATL) cells share the CD4⁺CD25⁺ phenotype with regulatory T (Treg) cells. However, it is still controversial whether ATL cells are Treg cells. The aim of the present study was to investigate the Treg nature of ATL cells obtained from peripheral blood and skin tumors in terms of their phenotype and function. By flow cytometry and immunohistochemistry, the expression of the Treg-associated molecule cytotoxic T lymphocyte-associated antigen (CTLA)-4 and Foxp3 was examined in freshly isolated circulating and skin-infiltrating tumor cells from 21 ATL patients with skin eruptions. The expression of CTLA-4 on freshly isolated circulating tumor cells was elevated in two of 15 patients, and Foxp3 was expressed intracytoplasmically at high levels in three of nine patients. In five of the patients examined, skin-infiltrating tumor cells bore variously elevated CTLA-4 with high Foxp3 expression. The potentiality of ATL cells as Treg cells was further addressed by stimulating ATL cells with anti-CD3/CD28 monoclonal antibodies and monitoring CTLA-4 expression. With the stimulation, even CTLA-4-low ATL cells expressed higher levels of CTLA-4 than normal CD4⁺CD25⁺ cells. To study function, ATL cells isolated from blood and skin tumors were tested for their ability to suppress the proliferation of autologous CD8⁺ T cells stimulated with allogeneic lymphocytes. Despite the expression of CTLA-4 and Foxp3, these tumors were incapable of suppressing the proliferation of autologous CD8⁺ T cells. ATL cells are phenotypically Treg cells in at least some patients, but lack immunoregulatory functions, at least toward CD8⁺ T cells. ( Cancer Sci 2008; 99: 98–106)