Changes of host immunity in relation to efficacy in liver cirrhosis patients with advanced hepatocellular carcinoma treated by intra-arterial chemotherapy

Purpose  It is known that tumors develop mechanisms to escape from the immune system and to inhibit antitumor responses. The aim of this study was to retrospectively assess changes of host immunity in relation to efficacy in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) treated by combined intra-arterial chemotherapy. Methods  Thirty-seven adult Japanese LC patients with aHCC were treated by intra-arterial combination chemotherapy. The control group was composed of 19 adult Japanese patients with chronic hepatitis C diagnosed by pathological examination of liver biopsy specimens. All control patients were stage 1 according to the fibrosis score of Desment. Results  Ten of the 37 patients (group PR) showed a partial response and 17 of the 37 patients (group SD) showed stable disease, but 10 of the 37 patients (group PD) showed no response. There were no significant differences in the percentage of Th1 cells between any of the groups either before or after chemotherapy. The percentage of Th2 cells was significantly higher in group PD before and after chemotherapy than in the control group (P < 0.05 by Tukey’s test). Although there was no significant difference, the percentage of Th2 cells was higher in group SD than in group PR. Conclusions  The percentage of Th2 cells increased in LC patients with aHCC as the efficacy of intra-arterial combination chemotherapy decreased. These results indicated that intra-arterial chemotherapy might be not useful for patients with aHCC, because it induces Th2 dominant host immunity.     

Changes of cytokines in cirrhosis patients with advanced hepatocellular carcinoma treated by intra-arterial chemotherapy

INTRODUCTION: Tumor necrosis factor (TNF) induces cancer cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand. Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes is also known to induce apoptosis. The aim of this study was to clarify changes of cytokines in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) receiving intra-arterial combination chemotherapy. METHODS: Twenty-one adult Japanese LC patients with aHCC received intra-arterial combination chemotherapy. The serum levels of TNF-alpha, soluble TNF receptor-I (sTNFr-I), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated. RESULTS: Thirteen of the 21 patients (group R) showed an objective response, while the other eight patients (group N) showed no response. The serum level of TNF-alpha was lower after chemotherapy than before chemotherapy in group N, but there was no difference of serum sTNFr-I levels between before and after chemotherapy and there were also no differences between the two groups. The serum sFas levels were higher after chemotherapy than before chemotherapy in group N, while there was no difference among groups. CONCLUSIONS: These results indicate that a high serum TNF-alpha level and a low serum sFas level might be important for successful combined arterial chemotherapy in LC patients with aHCC.     

Influence of the etiology of liver cirrhosis on the response to combined intra-arterial chemotherapy in patients with advanced hepatocellular carcinoma

Purpose  We have previously reported that intra-arterial chemotherapy prolongs the survival of patients with advanced HCC (aHCC); however, whether the response to intra-arterial chemotherapy depends on the etiology of underlying liver cirrhosis (LC) is still unknown. Aim  The aim of this study was to assess any influences of the etiology of LC on the response to combined intra-arterial chemotherapy for aHCC. Methods  A total of 53 adult Japanese LC patients (46 men and 7 women) with aHCC were treated with combined intra-arterial chemotherapy between 2002 and 2007 at our hospital. All of the patients had a Japan Integrated Staging (JIS) score of 3 or 4. Their tumors were inoperable according to computed tomography findings. Combined intra-arterial chemotherapy was administered via the proper hepatic artery every 5 days for 4 weeks and the chemotherapy regimen was continued for as long as possible. Results  There were 15 patients with HBV infection (B-LC group), 29 patients with HCV infection (C-LC group), and nine patients with alcoholic cirrhosis (A-LC group). The percentage of patients with a complete or partial response after 4 weeks of chemotherapy was 0% in the B-LC group versus 31.0% in the C-LC group and 44.4% in the A-LC group. The survival of the A-LC and C-LC groups was significantly longer than that of the B-LC group with the median survival time being 688, 368, and 211 days, respectively. Conclusions  Combined intra-arterial chemotherapy might be more effective for aHCC in patients with A-LC or C-LC than in patients with B-LC.     

Multimodal therapy for liver cirrhosis patients with advanced hepatocellular carcinoma

Purpose  

We have previously shown that continuous intra-arterial combination chemotherapy (IACC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with HCV-related liver cirrhosis (C-LC) or alcoholic liver cirrhosis (A-LC) than in patients with HBV-related LC (B-LC). However, it is still unknown whether IACC actually improves the prognosis of aHCC patients with liver cirrhosis (LC), because it is difficult to perform a randomized controlled trial for patients with a poor prognosis. The aim of this study was to retrospectively assess the influence of IACC on the prognosis of aHCC.     

Relationship of peripheral blood CD4-positive T cells to carcinogenesis in patients with HCV-related chronic hepatitis and liver cirrhosis

INTRODUCTION: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of type 1 T cell responses promotes antitumor immunity. However, detailed information on the immunological background of patients with HCC is still unknown. The objectives of this study were to evaluate the Th1/Th2 balance and to investigate the relation between carcinogenesis and host immunity in patients with chronic hepatitis C, HCV-related liver cirrhosis (LC), or HCC. PATIENTS/METHODS: The study population was 117 patients who had chronic inflammation due to HCV infection diagnosed from pathological examination of liver biopsy specimens, including 32 patients who had HCV-related LC with HCC. Apart from the patients with HCC, they were divided into the four subgroups based on the fibrosis score of Desment (stages 1-4). Blood samples were collected in the early morning before treatment. Flow cytometry was used to assess cytoplasmic IFN-gamma and IL-4 expression by peripheral blood CD4+ T cells, and the percentage of IFN-gamma+ and IL4- T cells (Th1) or IFN-gamma- and IL4+ T cells (Th2) was calculated before the start of each therapy. RESULTS: There were 20 patients in F1, 25 patients in F2, 19 patients in F3, 21 patients in F4, and 32 patients with HCC. In the F4 and HCC groups, Th1 cells tended to increase depending on the extent of fibrosis, although there were no significant differences between these groups and the other groups. In the HCC group, Th2 cells showed a significantly higher percentage than in the F1 or F3 groups. CONCLUSIONS: These results suggest that Th1 dominance is lost due to an increase of Th2 cells in HCC patients and that carcinogenesis might occur in patients with chronic HCV infection and increased level of Th2 cells.     

Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma

Purpose

We have previously reported that 24-h intra-arterial combination chemotherapy (IACC) prolongs the survival of patients with advanced hepatocellular carcinoma (aHCC). However, it has also been reported that 5-fluorouracil (5-FU) exacerbates liver damage in patients with liver cirrhosis (LC). The aim of this study was to clarify the hepatotoxicity of IACC in LC patients with aHCC.

Methods

Twenty-one adult Japanese patients (20 men and 1 woman) with aHCC and LC underwent IACC between 2004 and 2007 at our hospital. These patients showed multiple partial responses or stable disease, except for five patients who showed no response and three patients with tumors more than 30 mm in diameter. All patients had inoperable disease on the basis of computed tomography (CT) findings. IACC (leucovorin at 12 mg/h, cisplatin at 10 mg/h, and 5-FU at 250 mg/22 h) was delivered via the proper hepatic artery every 5 days for 4 weeks.

Results

Twelve patients were in Child-Pugh class A (group A), and nine were in class B (group B). The Child-Pugh score was significantly increased after chemotherapy compared with before chemotherapy in both groups. Serum albumin was significantly decreased after chemotherapy, and the number of patients with ascites also increased after chemotherapy. Serum type IV collagen and N-terminal propeptide of type III procollagen were significantly increased after chemotherapy, although there was no significant change in serum aminotransferases.

Conclusions

IACC might cause hepatotoxicity that induces fibrosis without releasing aminotransferases.     

Elevated Th22 as well as Th17 cells associated with therapeutic outcome and clinical stage are potential targets in patients with multiple myeloma

T helper (Th) cell imbalance plays important roles in tumor development and their effects in Multiple myeloma (MM) remain unclear. In the present study, we investigated the levels and clinical significance of Th22, Th17 and Th1 cells in patients with MM. Th subsets were examined by flow cytometry. Plasma IL-22, IL-17A and IFN-γ concentrations were measured by ELISA. AHR and RORC mRNA expression was examined by RT-PCR. Here, we found that the frequency of Th22 cells was significantly elevated in peripheral blood (PB) and bone marrow (BM) of newly-diagnosed MM patients, and recovered in complete remission patients after chemotherapy. The circulating Th17 cells accompanied by IL-17A levels were also up-regulated in MM patients and decreased after remission. We also found that there was a significantly positive correlation between Th22 and Th17 cells in MM patients. Moreover, the frequencies of Th22 and Th17 cells were higher in stage III than in stage I+II of MM. Our data demonstrated that Th22 and Th17 cells might be important therapeutic targets in multiple myeloma and could facilitate the effect of antitumor immunotherapy.     

Effects of Thermotherapy on Th1/Th2 Cells in Esophageal Cancer Patients Treated with Radiotherapy

Background: To investigate the effects of double radiofrequency hyperthermia on Th1/Th2 cells in esophagealcancer patients treated with radiotherapy. Materials and Methods: 22 patients with esophageal cancer weredivided into a radiotherapy group (10 cases) and a combined group (double radiofrequency hyperthermiacombined with radiotherapy group, 12 cases). Both groups received conventional radiotherapy using a cobalt-60therapy apparatus (TD60-66Gy/30-33F). Patients in the combined group also underwent double radiofrequencyhyperthermia (2F/W, 8-10F). Before and after treatment, Th1, Th2, Tc1 and Tc2 cells in peripheral bloodwere determined with flow cytometry. Results: In the radiotherapy group, Th1 cell contents before and afterradiotherapy were 17.5±5.26% and 9.69±4.86%, respectively, with a significant difference (p<0.01). The Th1/Th2ratio was significantly decreased from 28.2±14.3 to 16.5±10.4 (p<0.01). In the combined group, Th1 cell contentbefore radiotherapy was 15.9±8.18%, and it increased to 18.6±8.84 after radiotherapy (p>0.05), the Th1/Th2ratio decreasing from 38.4±36.3 to 28.1±24.0 (p>0.05). Changes in Th2, Tc1 and Tc2 cell levels were not significantin the two groups before and after therapy (p>0.05). Conclusions: Double radiofrequency hyperthermia canpromote the conversion from Th2 to Th1 cells, and regulate the balance of Th1/Th2 cells.     

自体肿瘤瘤苗对荷瘤鼠Th1、Th2型细胞因子及细胞毒作用的影响

目的研究经处理的H22肝癌细胞肿瘤瘤苗作为全细胞瘤苗对H22荷瘤小鼠体内Th1/Th2细胞比例和细胞因子的影响以及CTL的杀伤活性.方法用加重组白细胞介素2、重组粒细胞单核细胞集落刺激因子及福氏不完全佐剂制成疫苗,建立荷瘤小鼠模型,用51Cr释放法测定瘤苗免疫组、荷瘤组、正常组小鼠脾细胞对亲本H22肝癌细胞的杀伤活性;流式细胞仪检测单个核细胞中的Th1和Th2细胞,并取血检测血清中IL-10、IFN-γ水平.结果效靶比为200:1时,免疫小鼠脾细胞体外杀伤亲本H22肝癌细胞的杀伤率为38.3%,显著高于荷瘤组的13.6%,正常组的7.5%,以及对S180细胞的9.1%(P均＜0.05).瘤苗免疫组Th1细胞及Th1/Th2细胞的比值显著升高(P＜0.01),血清IFN-γ较对照组明显升高(P＜0.01);血清IL-10较对照组明显降低(P＜0.01).结论肿瘤细胞加小剂量IL-2和GM-CSF及佐剂组成的肿瘤细胞瘤苗可激发特异性细胞介导的免疫反应,改善抗肿瘤免疫反应.     

胃癌患者化疗前后Th1/Th2细胞因子的检测及其临床意义

目的 研究胃癌患者化疗前后CD4+T淋巴细胞中Th1、Th2类细胞因子的表达水平和Th1/Th2值的变化及其临床意义.方法 60例胃癌患者接受FOLFOX4方案化疗,应用流式细胞仪对化疗前后患者外周血特异性细胞因子的表达变化进行分析.结果 化疗后,全组胃癌患者外周血CD4+T淋巴细胞分泌的γ干扰素(IFN-γ)的表达水平为11.4%±5.0%,较化疗前升高(P＜0.05);白介素10(IL-10)的表达水平为3.6%±1.2%,较化疗前降低(P＜0.05);Th1/Th2(IFN-γ/IL-4)的值为3.4±1.0,与化疗前比较,无明显变化(P＞0.05).15例化疗后疗效为部分缓解的患者,外周血CD4+T淋巴细胞分泌的IFN-γ和肿瘤坏死因子-α(TNF-α)的表达水平分别为14.8%±8.0%和5.9%±2.0%,均较化疗前升高(均P＜0.05);Th1/Th2(IFN-γ/IL-4)的值为4.0±1.5,明显高于化疗前水平(P＜0.01).结论 有效的化疗可减轻患者机体的肿瘤负荷,降低Th1类细胞因子向Th2类细胞因子漂移的程度;但胃癌化疗的有效率较低,因此对胃癌化疗者,改善机体免疫功能仍是很重要的治疗措施.     

化疗对乳腺癌患者外周血Th1和Th2类细胞因子基因表达的影响

[目的]探讨化疗对乳腺癌患者Th1和Th2类细胞因子的基因表达的影响。[方法]采用逆转录聚合酶链反应（RT—PCR）技术，检测乳腺癌患者化疗前后外周血单个核细胞（PBMC）Th1和Th2类细胞因子mRNA表达水平的变化。[结果]乳腺癌组IL-2mRNA（4）、IL-12mRNA（5）阳性表达均较正常对照组（10，14）及良性乳腺肿瘤组（11，16）明显减少（P〈0．05）；IL-6mRNA（19）、IL-10mRNA（16）较正常对照组及良性乳腺肿瘤组（8，5）显著增加（P〈0．05）；正常对照组及良性乳腺肿瘤组Th1和Th2类细胞因子mRNA表达无显著性差异fP〉0．051。乳腺癌化疗3个周期后，IL-6mRNA（8／36）和IL-10mRNA（6／38）阳性表达均较化疗前（19／25，16，28）显著降低（P〈0．05）；IL-2mRNA（14／30）和IL-12mRNA（15／29）阳性表达均较化疗前（4，40，5／39）显著升高（P〈0．05）。[结论]化疗可使早期乳腺癌患者Th2类细胞因子的强势表达向Th1类逆转，改善患者的免疫状况。     

淋巴瘤与实体瘤患者Th1/Th2漂移状况比较

目的 比较淋巴瘤患者与实体瘤患者Th1/Th2的漂移状况,建立淋巴瘤生物治疗过程中免疫功能有效检测指标.方法 采集患者全血,淋巴瘤10例,实体瘤172例(其中上消化道恶性肿瘤36例;结直肠癌64例;肺癌43例,其他恶性肿瘤29例,健康对照30例.检测首先用刺激剂刺激细胞,增加细胞内因子表达,用荧光标记的特异性抗细胞因子单克隆抗体,特异性抗原抗体结合,最后应用流式细胞仪分析特异性细胞因子表达水平.结果 淋巴瘤与健康人外周血CD+4T细胞表达IFN-γ、IL-4阳性百分比以及IFN-γ/IL-4比值,差异均具统计学意义(P<0.05).淋巴瘤患者Th1/Th2(CD:胞内细胞因子INF-α/IL4)比值较上消化道肿瘤(食管和胃)明显降低差异具统计学意义(P=0.023);淋巴瘤与其他实体瘤(结直肠癌、肺癌、肾癌、乳腺癌及其他肿瘤)差异无统计学意义,但有下降趋势.结论 淋巴瘤患者免疫功能较实体瘤患者有降低趋势,免疫治疗是辅助化疗的必要途径,Th1/Th2(INF-α/IL4)比值有望成为有效的检测指标.

Abstract：

Objective To compare Th1/Th2 drift situation in patients with lymphoma with that in patients with solid tumors, and establish the effective immune function detectable criterion of lymphoma in biological treatment process. Methods The whole blood samples of 10 patients with lymphoma, 202 patients with solid tumors including 36 patients with upper digestive tract cancer, 64 colorectal cancer, 43 lung cancer and 20 the other malignancies, and 30 healthy persons as controls were collected. Stimulation agent was used to stimulate the cells in order to increase cell factor expression and fluorescent labeled specific anti-cytokine monoclonal antibody was used to bind with specific antigen. The expression of specific cytokines was detected by flow cytometry. Results Positive percentages of IFN- γ and IL-4 and ratio of IFN- γ /IL-4 in CD+4 T cells of human peripheral blood had statistically differences between in patients with lymphoma and controls (P < 0.05). The ratio of Thl/Th2 (CD+4 intracellular cytokine INF-α/IL-4) in patients with lymphoma was lower than that in patients with upper digestive tract cancers (esophagus and stomach cancers) (P = 0.023), however, had no statistical differences with that in patients with other solid tumors (colorectal, lung, kidney, breast and other tumors), but had a downward trend. Conclusion Immune functions in patients with lymphoma are lower than those in patients with solid tumors and immune treatment is a necessary to adjuvant chemotherapy. The ratio of Th1/Th2 (INF- α/IL-4) is expected to become effective detection criterion.     

Th1及Th2相关指标与鼻内翻性乳头状瘤的相关性

目的 探讨Th1及Th2相关指标与鼻内翻性乳头状瘤的关系.方法 选取62例鼻内翻性乳头状瘤患者为观察组,同时以同阶段的62名健康同龄人为对照组,然后将2组的血清Th1及Th2相关指标的表达水平进行比较,并比较观察组中不同Krouse分级患者的血清Th1及Th2相关指标的表达水平,并采用Logistic分析血清Th1及Th2相关指标与鼻内翻性乳头状瘤的关系.结果 观察组血清IL-2及IFN-γ的表达水平均低于对照组,其他血清Th1及Th2相关指标的表达水平均高于对照组,且不同Krouse分级患者的检测水平也存在明显差异.经Logistic分析血清Th1及Th2相关指标均与鼻内翻性乳头状瘤有密切的关系,P均＜0.05.结论 Th1及Th2相关指标均与鼻内翻性乳头状瘤有密切的关系,应加强对此类患者上述指标的监测与干预.     

宫颈癌患者血清Th1、Th2细胞因子表达水平及意义

目的 探讨宫颈癌患者血清Th1、Th2细胞因子表达水平及意义.方法 选取宫颈癌患者94例(观察组),同时选取健康女性90例作为对照组,检测两组患者干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)、IL-4和IL-6.结果 观察组IFN-γ、IL-2、IL-4和IL-6水平分别为(52.13±9.55)pg/ml、(38.70±8.96)pg/ml、(27.61±6.22)pg/ml和(32.16±7.81)pg/ml,均高于对照组(P﹤0.05);Ⅲ~Ⅳ期患者IFN-γ、IL-2、IL-4和IL-6水平高于Ⅰ期和Ⅱ期患者(P﹤0.05),Ⅱ期患者IFN-γ、IL-2、IL-4和IL-6水平高于Ⅰ期患者(P﹤0.05);不同分化程度患者IFN-γ、IL-2、IL-4和IL-6水平比较差异无统计学意义(P﹥0.05),有无淋巴结转移患者IFN-γ、IL-2、IL-4和IL-6水平比较差异无统计学意义(P﹥0.05).结论 宫颈癌患者Th1/Th2细胞因子动态平衡紊乱,可能在肿瘤的发生发展中有一定作用.     

三阴性乳腺癌细胞免疫状态和 Th1/Th2细胞因子的变化

目的：探讨三阴性乳腺癌的细胞免疫状态和 Th1/ Th2细胞因子的变化。方法：比较46例三阴性乳腺癌患者和60例非三阴性乳腺癌患者的临床资料,分析三阴性乳腺癌组、非三阴性乳腺癌组和对照组的细胞免疫状态及 Th1/ Th2细胞因子的变化。结果：三阴性乳腺癌和非三阴性乳腺癌两组相比,在发病年龄、月经状况、临床分期、组织学分级情况没有统计学差异（P >0.05）;在淋巴结转移和内脏转移方面有统计学差异（P<0.05）。乳腺癌患者 CD3、CD4、CD19 T 细胞亚群无改变,CD8和 CD69水平有变化,但后两者在三阴性乳腺癌和非三阴性乳腺癌组中没有统计学差异（P >0.05）。乳腺癌患者 IL -2分泌减少,IL -6、IL -10分泌高,存在 Th2漂移。结论：三阴性乳腺癌转移风险高,预后差。乳腺癌存在 Th1/ Th2失衡,但三阴性乳腺癌和非三阴性乳腺癌相比,并没有明显的 Th2优势,说明三阴性乳腺癌发病机制具有更为复杂的生物学因素。     

The critical role of Th1-dominant immunity in tumor immunology

To investigate the precise role of antigen-specific Th1 and Th2 cells in tumor immunity, we developed a novel adoptive tumor-immunotherapy model using OVA-specific Th1 and Th2 cells and an OVA gene-transfected tumor. This therapeutic model demonstrated that both antigen-specific Th1 and Th2 cells had strong antitumor activity in vivo with distinct mechanisms. However, immunological memory suitable for the generation of tumor-specific cytotoxic T lymphocytes was induced only when tumor-bearing mice received Th1 cell therapy, but not Th2 cell therapy. Thus it was strongly suggested that Th1-dominant immunity is critically important for the induction of antitumor cellular immunity in vivo. We also proposed that several immunomodulating protocols using interleukin (IL)-12, IL-12 gene, the natural killer T cell ligand !-galactosylceramide, or Th1 cytokine-conditioned dendritic cells might be useful strategies for the induction of Th1-dominant immunity essential for the development of tumor-specific immunotherapy.     

调节性T细胞及Th1/Th2细胞因子在急性白血病中的表达及意义

目的:探讨调节性T细胞（Tregs）及Th1/Th2型细胞因子在急性白血病发病中的作用。方法:采用流式细胞术检测37例急性白血病患者［包括急性髓细胞性白血病（acute myeloid leukemia,AML）24例,急性淋巴细胞白血病（acute lymphocytic leukemia,ALL）13例］及28例健康对照者外周血CD4+CD25+Foxp3+Tregs的比例,酶联免疫吸附法（ELISA）法检测血浆IL-2、IFN-γ、IL-10、IL-4和TGF-β水平。结果:AML和ALL患者外周血CD4+CD25+Foxp3+Tregs比例均高于健康对照组 (P＜0.05);AML及ALL患者血浆IL-4、IL-10和TGF-β水平均较健康对照组升高 (P＜0.05);IFN-γ水平较健康对照组降低 (P＜0.05);IL-2水平与健康对照组比较无明显差异 (P＞0.05)。结论:Tregs与Th1/Th2细胞因子同时参与了急性白血病的发生;急性白血病患者机体Th1/Th2细胞因子失衡,Th2占优势状态,这可能是导致急性白血病细胞免疫逃逸的原因之一;Tregs可能通过影响Th1/Th2细胞因子平衡参与急性白血病的发病。     

骨转移癌患者Th1/Th2亚群研究

目的：观察骨转移癌患者Ｔ淋巴细胞亚群中Ｔｈ１／Ｔｈ２的变化,为细胞因子免疫治疗提供依据。方法：应用放射免疫分析及酶联免疫分析检测３０例骨转移癌患者血清中ＩＬ－２、ＩＬ－４、ＩＬ－６、ＩＬ－１０、ＩＬ－１２的含量,检测外周血单个核细胞有或无植物血凝素（ＰＨＡ）存在情况下培养上清中ＩＬ－２、ＩＬ－４含量。结果：骨转移癌患者血清及培养上清中ＩＬ－２、ＩＬ－１２减少（Ｐ＜０．００１）,而ＩＬ－１０、ＩＬ－     

维吾尔族宫颈癌患者 Th1／Th2型细胞因子表达水平及临床意义

目的：评估宫颈癌及癌前病变患者免疫水平，进一步探讨维吾尔族宫颈癌患者血浆中Th1／Th2型细胞因子表达水平及临床意义。方法本研究收集宫颈癌、癌前病变（ CIN Ⅲ）患者及对照组外周血标本，使用ELISA法检测血浆中Th1型细胞因子IL－2、IFN－γ及Th2型细胞因子IL－4、IL－10的表达水平，绘制ROC曲线分析四种细胞因子在宫颈癌辅助诊断中的价值。结果与对照组相比，宫颈癌和癌前病变组Th1型细胞因子IL－2、IFN－γ表达量显著降低（P＜0．05），Th2型细胞因子IL－4、IL－10表达量显著升高（P＜0．05）；在宫颈癌组中，IL－10表达量随肿瘤分期逐渐升高（P＜0．05）；维吾尔族宫颈癌患者血浆IL－2表达量较汉族患者显著降低（ P＜0．05）；在区分宫颈癌组与对照组中，IL－2、IFN－γ、IL－4和IL－10的AUC分别为0．979、0．766、0．736和0．903。结论宫颈癌患者细胞免疫水平低下，体内发生Th1／Th2漂移，提示这可能是肿瘤细胞发生免疫逃逸的机制之一，Th1／Th2型细胞因子的检测对宫颈癌的辅助诊断具有一定参考价值，此外IL－2表达量的下调可能在维吾尔族宫颈癌发生发展过程中起到重要作用。     

Th17 cells and interleukin‐17 increase with poor prognosis in patients with acute myeloid leukemia

Although Th17 cells play crucial roles in the pathogenesis of many autoimmune and inflammatory disorders, their roles in malignancies are currently under debate. The role and mechanism of Th17 cells in patients with acute myeloid leukemia (AML) remain poorly understood. Here we demonstrated that the frequency of Th17 cells was significantly increased in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells from AML patients compared with healthy donors. Plasma levels of interleukin (IL)‐17, IL‐22, IL‐23, IL‐1β, IL‐6, and transforming growth factor (TGF)‐β1 were significantly increased in blood and bone marrow in AML patients compared with healthy donors. The in vitro experiments demonstrated that IL‐1β, IL‐6, IL‐23, but not TGF‐β1 promoted the generation and differentiation of Th17 cells from naive CD4⁺ T cells in humans. IL‐17A, a signature cytokine secreted by Th17 cells, induced the proliferation of IL‐17 receptor (IL‐17R)‐positive AML cells via IL‐17R, in which activation of PI3K/Akt and Jak/Stat3 signaling pathway may play important roles. In addition, combination of IL‐17A and IL‐22 significantly reduced the generation of Th1 cells and the production of interferon (IFN)‐γ from healthy donor or AML patient peripheral blood mononuclear cells. Patients with high Th17 cell frequency had poor prognosis, whereas patients with high Th1 cell frequency had prolonged survival. Combined analysis of Th1 and Th17 cell frequencies improved the ability to predict patient outcomes. In conclusion, Th17 cells play a crucial role in the pathogenesis of AML and may be an important therapeutic target and prognostic predictor.