Perioperative allogeneic blood transfusion exacerbates surgical stress-induced postoperative immunosuppression and has a negative effect on prognosis in patients with gastric cancer

The immunomodulative effect of perioperative allogeneic blood transfusion on host immunocompetence was studied in 109 patients with gastric cancer at various stages. Mitogen-induced lymphocyte blastogenesis, lymphocyte surface markers (specific for T, B, CD4, and CD8 populations), and the activity of natural killer (NK) cells were examined before surgery and then 2 and 4 weeks after surgery. The effects on host immunocompetence of transfusion alone, in the absence of any effect of surgical stress, were studied, preoperatively, in nine patients who received preoperative transfusion. Although a tendency towards a decrease in the posttransfusion activity of NK cells was observed, there were no statistically significant differences between pre- and posttransfusion levels. Mitogen-induced blastogenesis and the activity of NK cells were significantly impaired 2 weeks after surgery in transfused patients as compared to those in non-transfused patients with gastric cancer at stage III and stage IV, and postoperative survival was significantly lower in transfused as compared to nontransfused patients. These results indicate that perioperative allogeneic blood transfusion exacerbates surgical stress-induced postoperative immunosuppression and has a negative effect on prognosis in patients with gastric cancer. © Wiley-Liss, Inc.     

Influence of perioperative blood transfusion on the prognosis of patients with gastric cancer receiving anticancer chemotherapy

Background. The deleterious effect of blood transfusions on survival has been reported in patients with cancers of various organs. However, it remains unclear whether there is any adverse effect of blood transfusion when the patients are administered anticancer drugs after surgery for gastric cancers. Methods. Data from patients with gastric resection for advanced gastric cancer were retrospectively analyzed to determine the influence of perioperative blood transfusion on the survival rate. All patients were administered anticancer drugs (mitomycin C [MMC] and tegafur-uracil [UFT]). Sixty-nine (33%) of 208 patients received blood transfusion perioperatively, while 139 patients (67%) did not receive transfusion. Multivariate analysis of clinicopathologic prognostic factors, including blood transfusion, was performed. Lymphocyte subsets were measured to investigate the immunosuppressive effect of blood transfusion. Results. The 5-year survival rate was 48.8% in the 69 transfused patients and 66.9% in the 139 non-transfused patients (P < 0.01). Cox's multiple regression analysis showed that, when patients received anticancer drugs, perioperative blood transfusion was not a significant factor affecting survival after the gastric cancer surgery. However, the CD4/CD8 ratio at 3 months after the surgery was significantly lower in the transfused group than in the non-transfused group. Conclusion. Blood transfusion did not affect the survival of operated patients who received postoperative adjuvant chemotherapy. However, the finding that the ratio of CD4/CD8 after surgery was significantly higher in the non-transfused group than in the transfused group supports the notion that transfusion causes broad-spectrum immunosuppression. Received: December 13, 1999 / Accepted: March 15, 2000     

Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10

: To analyze prospectively the effects of blood transfusion administered during radiotherapy (RT) on the immune function of patients with locally advanced cervical cancer.

: In a total of 15 patients, 7 transfused and 8 untransfused, lymphocyte populations, including CD3+, CD4+, and CD8+ T-cell subsets, B cells (CD19+), and natural killer (NK) cells (CD56+, CD16+, CD3−) were studied before (i.e., time 0), during (i.e., times 1 and 2), and after (i.e., time 3) therapy. Expression of the early (CD25) and late (HLA-DR) activation markers on CD3+ T cells, the intracellular levels of perforin in CD8+ and CD56+ cells, and interferon (IFN)-γ, interleukin (IL)-2, and IL-4 in CD4+ and CD8+ T cells were also measured. NK cell cytotoxicity against the NK-sensitive target K-562 cells and CD8+ T-cell-directed cytotoxicity against OKT3 hybridoma cells were also assessed. Finally, the plasma levels of the immunoregulatory cytokine IL-10 were analyzed by enzyme-linked immunosorbent assay.

: The mean absolute number of all lymphocyte subsets compared with pretreatment levels decreased significantly during RT of both transfused and untransfused patients (p >0.001), with no detectable differences between the two groups in terms of total lymphocytes or relative numbers of CD3+ and CD4+ T cells, CD56+ NK cells, or CD19+ B cells. In contrast, concomitant with an inversion of the CD4/CD8 ratio, a significant increase in the number of CD8+ T cells at time 2 and CD3+ T cells, CD8+ T cells, and NK cells at time 3 was found in the transfused patients compared with the untransfused group. The percentages of CD25+/CD3+ T cells and HLA-DR+/CD3+ T cells increased during RT of the untransfused patients, but CD3+ T cells showed decreased CD25 expression and increased HLA-DR expression in the transfused group. An increase of CD8+ IFN-γ+ T cells with a concomitant decrease in CD8+ IL-2+ T cells was found in the transfused vs. untransfused group, and no differences were noted in the percentage of CD4+ IFN-γ+ T cells and CD4+ IL-2+ T cells. The proportion of perforin-positive CD8+ and CD56+ cells was higher in the transfused group than in the untransfused group. However, CD56+ cells and CD8+ T cells from the transfused patients showed markedly diminished cytotoxic function. Finally, IL-10 was detected only in the plasma of the transfused patients.

: Blood transfusion during primary RT for cervical cancer profoundly alters the magnitude and characteristics of radiation-induced immunosuppression. Elevated serum IL-10 in transfused patients may play a role in the disregulation of lymphocyte function, in particular, the depression of NK- and T-cell cytotoxicity. Investigation of alternatives to blood transfusion during RT that do not diminish host immunity is warranted.     

Blood transfusion and the prognosis of patients with gastric cancer

A retrospective analysis was undertaken of the association between blood transfusion and long-term results for 218 patients with stage III gastric cancer who were curatively treated by partial gastrectomy. One hundred and fifty-two patients received blood transfusion within the perioperative period. The postoperative 5-year survival rates were 49.3% for the transfused patients and 62.1% for the non-transfused patients (P less than 0.05). Furthermore, the postoperative survival of patients who had been transfused preoperatively was significantly lower than that of the non-transfused patients. The preoperatively transfused group of patients were found to have tumors that were larger than those of the non-transfused group. On the basis of the above data, it appears that the prognosis of patients with advanced gastric cancer is poorer when such patients receive preoperative blood transfusion than when patients do not receive transfusions, and that this adverse effect in the transfused patients is probably attributable to the larger size of their tumors, even though the stage of advancement of gastric cancer is the same in both groups of patients.     

肺癌患者外周血 T- 淋巴细胞亚群 NK 细胞的基线数值及其与预后的关系*

目的:对比肺癌患者与健康者之间淋巴细胞亚群差异,评估肺癌患者外周血T 淋巴细胞亚群及自然杀伤细胞（NK）之基线值与预后的关系。方法:收集2006年2 月至2013年3 月就诊于天津医科大学肿瘤医院病例资料完整的肺癌患者105 例,其中非小细胞肺癌（NSCLC ）86例、小细胞肺癌（SCLC）19例,另选健康对照35例,对比接受治疗前肺癌患者和健康对照者外周血中的CD3+T 细胞、CD4+T 细胞、CD8+T 细胞及NK细胞所占百分比,并回顾性分析86例NSCLC 患者初治时外周血淋巴细胞亚群与预后的关系。结果:肺癌患者外周血CD3+T 细胞、CD4+T 细胞、NK细胞及CD4/CD 8 比值均明显低于健康对照组（P = 0.011,P = 0.007,P <0.001,P=0.025）,而CD8+T 细胞比例高于健康对照组（P = 0.013）。 当CD8+T ≥ 31.8% 及CD4/CD 8< 1.28时NSCLC 患者可以获得一个更长的OS（中位OS分别为36.2 m vs . 20.0 m ,P = 0.010;30.8 m vs . 20.0 m ,P = 0.035）。 而CD3+T 细胞、CD4+T 细胞及NK细胞百分比对NSCLC 患者预后无显著影响。结论:外周血CD8+T 细胞基线水平较高的NSCLC 患者生存较长,此基线水平可能对NSCLC 患者预后有指示作用。      

Effects of Allogeneic Blood Transfusion in Patients with Stage II Colon Cancer

The aim of the present study was to determine whether allogeneic red blood cell transfusions showed adeleterious effect and what might be preoperative risk factors for blood transfusion in patients with TNM stageII colon cancer. Total 470 patients who fulfilled inclusion criteria were selected for a further 10-year followupstudy. We found that there were statistical significance between non-transfused and transfused group inmortality (P=0.018), local recurrence (P=0.000) and distant metastasis (P=0.040). Local recurrence and distantmetastasis between 1 to 3 units and more than 3 units group did not show any significant differences. There wasno difference in survival rate between non-transfused and 1 to 3 units group (log rank =0.031, P=0.860). Thedifference between different blood transfusion volume in transfused patients was found (78.77% vs 63.83%,P=0.006). Meanwhile, the significant difference of survival rate was existed between non-transfused group andmore than 3 units group (84.83% vs 63.83%, P=0.002 ). Univariate analysis showed the following 3 variablesto be associated with an increased risk of allogeneic blood transfusions: preoperative CEA level (P<0.05),location of tumor (P<0.01) and diameter of tumor (P<0.01). Multivariate analysis revealed that location of tumorand diameter of tumor are two independent factors for requirement of perioperative transfusions. Therefore,allogeneic transfusion increase the postoperative tumor mortality, local recurrence and distant metastasis inpatients with stage II colon cancer. The postoperative tumor mortality, local recurrence and distant metastasiswere not associated with the blood transfusion volume. The blood transfusion volume was associated with thesurvival rate. Location of tumor and diameter of tumor were the independent preoperative risk factors for bloodtransfusion.     

食管胃交界部腺癌根治性手术对细胞免疫的影响

目的:探讨进展期食管胃交界部腺癌(AEGJ)患者围手术期外周血中淋巴细胞亚群及CD4+CD25+T细胞和程序性细胞死亡1（PD-1）在T淋巴细胞中表达的变化,了解根治性手术创伤对机体细胞免疫功能的影响及机制。 方法:126例进展期食管胃交界部腺癌行开腹根治性R0切除+D2淋巴结清除术,同期体检志愿者87例为对照组。应用流式细胞仪检测对照组和治疗组术前、术后1天、术后3天、术后7天和术后9天外周血CD3+、CD3+CD4+、CD3+CD8+、CD4+CD25+T细胞计数和PD-1在T细胞中的表达水平。结果:治疗组术前和对照组相比较,CD3+、CD3+CD4+T细胞均显著降低（P<0.05）,而CD4+CD25+T细胞和PD-1在CD4+、CD8+T细胞的表达比例均显著增高（P<0.05）。CD4+CD25+T细胞的比例在术后1天迅速下降至谷底,随后逐渐升高,于术后7天达顶峰,然后再次下降。CD4+PD-1+T细胞的比例在术后显著增加:术后第1天达到最大值,然后逐渐下降,但在术后第7天仍显著高于术前。 CD8+PD-1+T细胞的比例则在术后逐渐增加,到术后7天达高峰。结论:食管胃交界部腺癌手术创伤可能是通过各种细胞因子导致CD4+PD-1+T细胞比例改变,进而调节T淋巴细胞亚群比例,抑制细胞免疫能力。     

胰腺癌患者围手术期T细胞亚群和NK细胞活性的动态观察

目的探讨胰腺癌患者围手术期外周血T细胞亚群、NK细胞的变化及其临床意义.方法采用流式细胞术法分别测定58例胰腺癌患者手术前后外周血T细胞亚群CD4 、CD8 和NK细胞的水平,并与健康对照组比较分析.结果胰腺癌组治疗前外周血CD4 、CD4 /CD8 和NK细胞均降低,而CD8 增高,与对照组比较差异有显著性(P<0.01);且与淋巴结转移和肿瘤临床TNM分期有显著相关性.行根治性手术组术后CD4 、CD4 /CD8 和NK细胞均有显著性增高(P<0.05),CD8 显著性降低(P<0.05);而姑息性手术组CD4 、CD4 /CD8 和NK细胞则无显著性增高(P>0.05),CD8 无显著性降低(P>0.05).结论胰腺癌患者血清T细胞亚群和NK细胞的变化与肿瘤的浸润转移和病程有关,检测胰腺癌患者血清T细胞亚群和NK细胞的变化,有助于评估患者的疗效和预后.     

围手术期输血对结肠癌根治术后复发率影响

作者对129例结肠癌根治术后复发率进行回顾性总结.发现围手术期输血确能增高结肠癌根治术后复发率.输血组复发率为29.14％,未输血组复发率为零.二组数字有显著性差异.输血能增高结肠癌根治术后复发率的机理是宿主免疫系统的抑制.作者建议结肠癌根治术一般情况下应不输血.     

晚期肺腺癌患者一线化疗后T淋巴细胞亚群变化及临床意义

背景与目的机体的免疫功能异常与恶性肿瘤的发生、发展、转移及预后密切相关。T淋巴细胞亚群是反映细胞免疫功能的重要指标之一。本实验研究晚期肺腺癌患者一线化疗后外周血T淋巴细胞数量的动态变化,探讨化疗后机体免疫状态变化的动态过程,为制定化疗联合免疫治疗方案提供实验依据。方法 49例经病理学确诊的IIIb期-IV期肺腺癌患者,与33例正常人比较外周血T淋巴细胞数量。然后患者随机进入2个实验组,分别采用培美曲塞、顺铂联合方案及多西他赛、顺铂联合方案化疗,应用流式细胞仪检测化疗前后不同时间点淋巴细胞的组成。结果肺癌患者的CD3+、CD3+CD4+、CD4+CD25+等T细胞的数量与健康对照组比较存在差异,P值分别为0.012,0.034和0.006;化疗后第4天及第7-10天CD3+、CD3+CD4+比例升高,至第21天逐渐恢复至治疗前水平;2个化疗组比较CD3+细胞比例均升高,而培美曲塞组第4天CD3+、CD3+CD4+、CD4+/CD8+升高,CD3+CD8+及CD8+CD28-比例降低,差异均具有统计学意义。部分缓解患者较早期疾病进展患者的第4天及第7-10天CD3+CD4+细胞升高;第4天CD3+CD8+、CD8+CD28-细胞降低。结论晚期肺腺癌患者免疫功能处于抑制状态。化疗后第4天免疫功能得到一定程度恢复,至第21天恢复至治疗前水平。培美曲塞似乎对化疗后短期内免疫功能的改善有更明显的作用。化疗后免疫格局的改变可能与预后有关。     

Perioperative blood transfusion in hepatocellular carcinomas: influence of immunologic profile and recurrence free survival

BACKGROUND: The postoperative recurrence of hepatocellular carcinomas (HCC) associated with perioperative blood transfusion has been the subject of controversy. The authors prospectively investigated the relation between perioperative allogeneic blood transfusions, the recurrence free survival, and the immunologic profiles of patients with HCC who had undergone curative hepatic resections. METHODS: One hundred eight patients were divided into two groups: a transfused group (n = 53) and a nontransfused group (n = 55), according to their perioperative transfusion history. The subsets of lymphoid cells, natural killer cell activity and the phytohemagglutinin (PHA) response were all measured preoperatively, and at 1, 2, and 4 weeks and at 3 and 6 months after the hepatectomy. The recurrence free survival rate then was compared between these two groups. RESULTS: There were no significant differences between these two groups with respect to histologic findings, clinical stage, type of resection, pathologic data, and the recurrence free survival rate. Postoperative levels of the CD8 in the transfused group were elevated as compared with the nontransfused group, and the PHA response of the transfused patients was significantly increased at 7 postoperative days. Natural killer cell activity of the transfused patients was decreased at 7 postoperative days, as compared with the nontransfused patients, but there was no significant difference. CONCLUSIONS: Although allogeneic blood transfusion may have immunosuppressive effects, perioperative blood transfusions did not influence the cancer free survival rate in patients with hepatocellular carcinoma.     

全胸镜肺叶切除术在早期非小细胞肺癌治疗中的应用研究

目的 研究全胸镜肺叶切除术(VATS)与开胸肺叶切除术(PL)治疗早期非小细胞肺癌(NSCLC)的疗效、彻底性及安全性.方法 选取早期NSCLC患者106例,依照随机数字表法1:1分为VATS组与PL组,每组各53例.VATS组行VATS治疗,PL组行PL治疗.观察两组手术时间、淋巴结清扫数、术中出血量、输血量、术后引流时间、总引流量、下床活动时间等手术指标,术前及术后7 d TNF-α、CRP、IL-6、CD3+、CD4+、CD8+及CD4+/CD8+等水平,疼痛程度,术后并发症、复发及1~3年生存情况.结果 VATS组术中出血量、治疗期间总输血量、下床活动时间以及疼痛程度评分均低于PL组,差异均有统计学意义(P<0.05).VATS组术后7 d患者血清中的CRP、IL-6、TNF-α与术前的差值均低于PL组各指标手术前后的差值,差异有统计学意义(P<0.05).VATS组术后7 d患者血清中的CD3+、CD4+、CD8+及CD4+/CD8+与本组术前的差值均高于PL组手术前后各指标的差值,差异有统计学意义(P<0.05).VATS组术后并发症发病率(15.09%)低于PL组(35.85%)(P<0.05);VATS组术后1~3年生存率高于PL组(P<0.05).结论 VATS治疗NSCLC创伤小,对免疫系统影响小,疗效显著,治疗彻底安全,值得应用于临床.     

Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck.

PURPOSE: Apoptosis of circulating CD8+ T cells seen in patients with squamous cell carcinoma of the head and neck [SCCHN (Hoffmann T, et al. Clin Cancer Res 2002;8:2553-62)] suggested a possibility of lymphocyte imbalance. Therefore, absolute numbers and percentages of lymphocyte subsets were examined in the peripheral blood of SCCHN patients and controls. EXPERIMENTAL DESIGN: Venous blood was obtained from 146 patients with SCCHN and 54 normal volunteers. Absolute numbers of CD3+, CD4+, and CD8+ T lymphocytes were determined using fluorobeads in a flow cytometry-based technique. Percentages of T lymphocyte subsets were also evaluated by flow cytometry. The patients were grouped at the time of blood draw [active versus no evidence of disease (NED), type of therapy administered, and the length of follow-up]. RESULTS: Patients with SCCHN had significantly lower absolute numbers of CD3+ CD4+, and CD8+ T cells than normal controls. However, no differences in the percentages of T-cell subsets between patients and normal controls were observed. Patients with active disease had significantly lower CD3+ and CD4+ T-cell counts than those with NED. Patients who had NED after surgery and radiotherapy had the lowest T-cell counts among the NED cohort. Patients who had NED for >2 years did not recover their T-cell counts, and the T-cell imbalance was evident many years after curative surgery. The tumor-node-metastasis (TNM) stage or site of the disease was not related to the absolute T-cell count. Patients with recurrent disease at the time of blood draw tended to have the lowest CD4+ T-cell counts. CONCLUSIONS: Patients with SCCHN have altered lymphocyte homeostasis, which persists for months or years after curative therapies.     

细胞因子诱导的杀伤细胞对恶性肿瘤患者细胞表型的影响

目的:探讨细胞因子诱导的杀伤细胞(cytokine induced killer cells,CIK cells)治疗对恶性肿瘤患者淋巴细胞亚群的影响,对比接受CIK细胞免疫治疗前后,培养细胞表型及患者淋巴亚群的变化.方法:选取辽宁省肿瘤医院手术、放化疗治疗结束1个月以上或无法进行以上治疗,单纯接受4个周期CIK细胞免疫治疗的恶性肿瘤患者67名入组.应用流式细胞术检测分析接受4周期CIK细胞免疫治疗前后患者淋巴细胞CD3+CD4+、CD3+CD8+、CD4+/CD8+、CD3+CD56+、CD3-CD56+、CD3+PD1+亚群的变化情况.同时对各次输注细胞表型(CD3+CD4+、CD3+CD8+、CD3+CD56+)进行检测,观察其变化.结果:患者接受4周期CIK细胞免疫治疗后,与治疗前相比,淋巴细胞CD3+CD4+、CD3+CD8+、CD4+/CD8+、CD3+CD56+亚群略有升高,但无统计学差异.CD3-CD56+、CD3+PD1+亚群无明显变化.值得注意的是,输注细胞表型与第一次培养后相比,第二次、第三次的CIK细胞CD3+CD8+、CD3+CD56+表型呈阶梯型上升,结果有统计学差异.第三次与第四次无明显变化.结论:CIK细胞免疫治疗能稳定肿瘤患者免疫状态.接受过CIK细胞回输的患者,再次抽取外周血进行培养时,可增加体内CD3+CD56+前体细胞增殖和定向分化的能力,有望得到远期获益.     

外周血淋巴细胞亚群水平变化在鼻咽癌中的意义

目的 探究外周血淋巴细胞亚群水平变化在鼻咽癌(NPC)中的意义.方法 选取NPC患者60例为试验组,选取健康体检者30例为对照组.采用流式细胞仪检测试验组治疗前后和对照组的外周血中CD3+、CD4+、CD8+细胞亚群及自然杀伤细胞(NK)水平;采用免疫组化法和Western Blot检测试验组治疗前后肿瘤组织中白细胞介素-21(IL-21)蛋白表达水平.结果 治疗前,试验组外周血中CD3+、CD4+、CD4+/CD8+及NK细胞水平明显低于对照组(P﹤0.01),CD8+细胞水平明显高于对照组(P﹤0.01);治疗后,试验组外周血中CD4+、CD4+/CD8+和NK细胞水平均较本组治疗前明显上升(P﹤0.01),CD8+细胞水平较本组治疗前明显下降(P﹤0.01);治疗后,早期NPC患者的总缓解率高于晚期NPC患者(P﹤0.05);免疫组化法和Western Blot检测结果显示,治疗前,NPC患者肿瘤组织中IL-21蛋白的阳性表达率及表达水平均高于治疗后(P﹤0.05).结论 NPC患者外周血中淋巴细胞亚群及NK细胞的检测对鼻咽癌的早期诊断及疗效评判具有重要意义.     

老年肾癌患者血清T淋巴细胞亚群变化对其预后及生存的影响

目的:探讨分析老年肾癌患者血清T淋巴细胞亚群变化对其预后及生存的影响。方法:选择2013年4月至2015年3月我院收治的78例老年肾癌患者，再选择同期来我院体检的健康人群50例作为对照组，术前以及术后2周采用流式细胞技术检测肾癌患者外周血T淋巴细胞亚群水平变化情况，并与对照组比较。对患者进行随访分析，采用Kaplan-Meier生存分析术后不同T淋巴细胞亚群水平对患者生存预后的影响。结果:肾癌组患者术前、术后2周外周血CD3+、CD4+以及CD4+/CD8+水平均显著低于对照组（P＜0.05）。肾癌组术后2周外周血CD3+、CD4+以及CD4+/CD8+水平较术前有显著升高（P＜0.05）。CD3+>48%肾癌患者总体生存情况显著优于CD3+≤48%患者（P＜0.05）。CD4+>30%肾癌患者总体生存情况显著优于CD4+≤30%患者（P＜0.05）。CD8+>25%肾癌患者总体生存情况与CD8+≤25%患者生存情况无差异（P＞0.05）。CD4+/CD8+>1.0肾癌患者总体生存情况显著优于CD4+/CD8+≤1.0患者（P＜0.05）。结论:老年肾癌患者存在广泛的细胞免疫功能紊乱现象，手术治疗后能够有效去除瘤负荷而从一定程度上逆转免疫功能，术后免疫功能指标可反映患者预后情况，免疫功能状态越差的患生存情况越差。     

肿瘤患者外周血免疫细胞亚群和有关细胞因子含量的相关性研究

目的:评价血液中CD3+、CD4+、CD8+、CD19+、自然杀伤（NK）细胞含量和细胞因子肿瘤坏死因子（TNF）、白介素-2（IL-2）、IL-6、IL-10的相关性。方法:对80例不同肿瘤患者和20例健康对照者进行细胞亚群和细胞因子检测。使用流式细胞仪测定样本外周血CD3+、CD4+、CD8+、NK、CD19+细胞比例,同时使用酶联免疫吸附试验测定外周血中TNF、IL-2、IL-6、IL-10水平。应用配对资料t检验分析肿瘤患者和正常对照者的细胞亚群和细胞因子有无差异,应用直线相关性t检验分析各细胞亚群和细胞因子之间有无线性相关。结果:肿瘤患者CD8+细胞含量高于正常对照者,NK细胞含量低于正常对照者,血液中CD3+细胞含量和细胞因子TNF、IL-2、IL-6、IL-10均无相关性,CD4+、CD8+细胞含量和IL-2线性相关,NK细胞含量和IL-2、IL-10线性相关,CD19+细胞含量和IL-6线性相关（但差异无统计学意义）。结论:肿瘤患者细胞免疫状况和正常人有统计学差异,细胞因子未发现统计学差异;免疫细胞亚群和细胞因子有一定线性相关。     

Impact of topotecan-based chemotherapy on the immune system of advanced ovarian cancer patients: an immunophenotypic study

The effects of topotecan-based chemotherapy (CT) on peripheral blood lymphocyte (PBL) subsets were evaluated in ovarian cancer patients. Fourteen patients with epithelial ovarian cancer, at the diagnosis or relapsed after platinum-based CT, were treated with: a) topotecan in association with carboplatin and taxanes as first line CT; b) topotecan alone or c) topotecan in association with carboplatin both as second line of treatment after platinum. The phenotype of PBL was determined before starting treatment and immediately before each CT course by flow cytometric analysis. Before starting CT, the absolute number of lymphocytes and the CD2+, CD3+, CD4+ subsets were significantly lower in pre-treated patients and not significantly altered in CT-naive patients with respect to a cohort of 20 healthy donors utilized as control. Lymphocytes co-expressing CD4+/CD8+ were significantly higher in both subgroups of patients than in normal donors. CD4+/CD45RA+ and CD4+/CD45RO+ subsets were significantly decreased in pre-treated patients and normal in CT-naive patients. CD3+/HLA-DR+ T cell population significantly increased in CT-naive patients at baseline. During CT and after its discontinuation, no relevant changes were recorded for both subgroups of patients with respect to the baseline in lymphocyte absolute count, CD2+, CD3+, CD4+, CD4+/CD45RO+ subsets, while CD4+/CD45RA+ subpopulation was significantly decreased in CT-naive patients. CD8+, CD19+, CD20+, CD16+, CD56+, CD2+/CD25+ subsets did not differ statistically comparing to normal donors both at baseline and during CT. The treatment was well tolerated and no patient developed non-neutropenic infection. Topotecan-based therapy does not have a negative impact on PBL in either CT-naive or in pretreated ovarian cancer patients. This information should be considered when utilizing topotecan with other anticancer drugs in the adjuvant setting as well as when dose-intensification of topotecan with stem cell support is planned.     

全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响

目的探讨全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响。方法收集接受肺癌根治术的84例患者的病历资料,按照患者所行麻醉方式的不同对其进行分组,单纯行全麻者42例归为对照组,行全麻复合硬膜外麻醉者42例纳入观察组,分析不同麻醉方式对患者外周血T细胞亚群及NK细胞活性影响的差异性。结果术后24 h观察组与对照组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、NK细胞水平均较术前明显降低,且术后24 h相比对照组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、NK细胞水平,观察组患者以上指标水平明显更高(P<0.05)。术后1周2组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+水平与术前相比并无明显差异(P>0.05),但NK细胞水平较术前明显降低(P<0.05),且术后1周相比对照组患者,观察组患者的NK细胞水平更高(P<0.05)。观察组患者的术后苏醒时间、术后拔管时间、自主呼吸恢复时间均明显短于对照组患者,2组差异有统计学意义(P<0.05)。结论相比单纯全麻,全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响更小,有助于患者术后的恢复。     

CD8+CD28− cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients

Aim To evaluate the CD8+CD28? and CD4+CD25+ regulatory T (Treg) cells in addition to other some lymphocyte subgroups in peripheral blood of advanced stage lung cancer patients. Methods The study group (n = 28) comprised chemotherapy and radiotherapy naïve patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The control group (n = 22) consisted of age- and sex-matched healthy volunteers. Flow cytometry was used to count T cells, natural killer (NK) cells and CD4+CD25 Treg cells, and for CD8+ T cell subgroup analysis. Flow cytometry was performed and annexin V binding was used for apoptotic cell evaluation. Results In patient group, the percentage of CD8+CD28? cells among lymphocytes was elevated, and there was also an increase in the CD28?/CD28+ cell ratio among CD8 lymphocyte population. The distribution of CD8 cells was different in lung cancer patients when compared with the control group. The absolute count of CD4+CD25^bright cells and the percentages of these cells among total lymphocytes were higher in the patient group. The Annexin V(+) cell percentages among CD8+CD28? and CD8+CD28+ lymphocytes were higher in the patient group than in the control group. No differences were found between the NSCLC and SCLC patients with respect to the hematological parameters and the distribution of lymphocyte subgroups. In NSCLC patients, the percentage of CD8+CD28? cells among the lymphocyte population was higher in patients with stage IV than those with stage III. Conclusion These findings may reflect the possibility of tumor-induced immunosuppression and they should be complemented with further studies.