姜黄素抑制CD44+结肠癌细胞增殖的体外实验研究

目的:探讨姜黄素能否抑制CD44+ 结肠癌细胞的增殖。方法:MTT 法检测姜黄素处理的结肠癌细胞增殖情 况,Real-time PCR 检测姜黄素处理的结肠癌细胞CD44 mRNA 的表达水平,流式细胞术检测姜黄素处理的结肠癌细胞表面 CD44 的表达水平,磁珠分选方法分离得到结肠癌细胞中CD44+ 细胞和CD44- 细胞, MTT 法观察姜黄素对两种细胞增殖情况 的影响。结果:姜黄素可抑制结肠癌细胞HCT116 和HT鄄29 增殖,Real鄄time PCR 和流式细胞术均证明姜黄素可导致结肠癌细 胞CD44 表达下调,磁珠分选方法获得CD44+的结肠癌细胞并应用姜黄素处理后,结果提示姜黄素可抑制CD44+细胞增殖。结 论:姜黄素可通过抑制结肠癌肿瘤干细胞增殖而降低结肠癌复发和转移,有望成为结肠癌治疗的辅助性药物。     

CD44+/CD24-细胞在乳腺癌组织及细胞系中的数量与分布

目的 检测CD44+/CIY24-细胞在乳腺癌组织及细胞系中的分布及数量,探讨其与乳腺癌常用标志物表达和乳腺癌分子亚型的关系.方法 采用免疫组织化学SP双染及单染法,分别检测了60例乳腺浸润性导管癌中的CD44及C1724的共表达情况和ER、PR、HER2、人雌激素诱导蛋白PS2、bcl-2、nm23的单独表达情况,同时检测了三种乳腺痛细胞系(MCF-7、MDA-MB-468及MDA-MB-231)中CD44及CD24的表达情况.结果 不同病例标本中CD44+/C1724-细胞的数量差异较大,分布无明显规律,总阳性率为65.0%;CD44+/CD24-细胞数量与患者年龄、肿瘤大小、淋巴结转移情况及ER、PR、HER-2、人雌激素诱导蛋白PS2、bcl-2、nm23表达情况无关(P均>0.05);CD44+/CD24-细胞数量与乳腺癌分子亚型无关.CD44+/CIY24-细胞在MCF-7、MDA-MB-468及MDA-MB-231细胞系中的比例分别为<1%、5%及>80%.结论 CD44+/CD24-细胞存在于部分乳腺癌组织及细胞系中,其数量及分布与乳腺癌的分子亚型和临床病理参数无直接关系.     

肿瘤干细胞相关标记物CD44及CD24在乳腺癌中的表达及其意义

目的探讨肿瘤干细胞相关标记物CD44及CD24在乳腺癌组织中的表达特点、CD44+/CD24-细胞与HER-2、ER、PR、CK5/6表达的相互关系及其与临床病理因素的关系。方法采用免疫组化SP单染及双染法检测42例乳腺导管原位癌及126例乳腺浸润性导管癌组织中CD44及CD24的表达情况,检测126例乳腺浸润性导管癌组织中HER-2、ER、PR、CK5/6表达状况以进行免疫分型。结果 (1)CD44阳性定位于癌细胞膜。在浸润癌中阳性率为56.3%,在导管原位癌中阳性率为85.7%。两者差异有显著性意义(P<0.05)。在不同分化程度的乳腺浸润性癌中,CD44阳性率分别为69.2%、58.1%及44.7%,差异有显著性意义(P<0.05)。(2)CD24阳性表达于非癌性乳腺组织中小管的腔缘;在癌组织中除腔缘阳性外,可出现膜质阳性。在浸润癌中阳性率为32.5%,在导管原位癌中阳性率为64.3%。两者差异有显著性意义(P<0.05)。(3)126例浸润性导管癌中CD44+/CD24-者65例,占51.6%;CD44+/CD24-阳性细胞在Luminal A型为47.5%、Luminal B型为42.9%、HER-...     

乳腺癌中CD44~+/CD24~-表型及乳腺癌分子亚型的分布及意义

目的探讨CD44+/CD24-表型在乳腺癌中的临床病理意义和乳腺癌分子亚型在中国人群中的分布。方法回顾分析217例乳腺癌患者,根据ER、PR、Her-2及CK5/6的水平划分为5个分子亚型。应用双重免疫组织化学检测其CD44/CD24双染的情况,分析CD44+/CD24-表型在乳腺癌中表达情况及其与临床病理的相关性;分析乳腺癌分子亚型在中国人群中的分布情况。结果 217例乳腺癌病例中,luminal A型130例,luminal B型15例,Her-2过表达型21例,basal-like型29例,Normalbreast-like型22例。CD44+/CD24-表型在所有乳腺癌阳性表达率为38%。CD44+/CD24-表型与患者年龄、肿瘤大小、组织分级、淋巴结转移等无关(P0.05)。结论乳腺癌干细胞表型(CD44+/CD24-)在乳腺癌中只占一小部分,在人类乳腺癌中CD44+/CD24-表型无临床病理意义;5种分子亚型中luminal A型所占比例最高,其他亚型所占比例较低。     

人血清白蛋白对近端肾小管上皮细胞骨调素和CD44表达的影响

目的：研究人血清白蛋白能否刺激人近端肾小管上皮细胞产生骨调素（OPN）和CD44。方法： 用人血清白蛋白刺激人近端肾小管上皮细胞系（HK-2细胞），分不同时间（0-48 h）、不同浓度（0.1-10 g/L）两组，以RT-PCR方法分别检测两组细胞表达的OPN mRNA，以Western blotting分别检测两组细胞表达的OPN。用免疫荧光法、激光共聚焦显微镜观察1 g/L的人血清白蛋白刺激HK-2细胞24 h、48 h后OPN、CD44的表达。结果： 人血清白蛋白刺激HK-2细胞上调表达OPN mRNA和蛋白，呈时间和剂量相关性。CD44的表达与OPN同步。 结论： 人血清白蛋白可刺激HK-2细胞表达OPN与CD44。     

STAT3抑制剂Stattic激活ERK通路诱导THP-1细胞IL-8的产生及细胞凋亡

目的观察信号转导子与转录激活子3(STAT3)抑制剂Stattic对THP-1细胞产生白细胞介素8(IL-8)和细胞凋亡的影响,并探讨其机制。方法采用(0、 1、 5、 10、 15、 20)μmol/L Stattic处理THP-1细胞0、 1、 3、 6、 12、 24h,实时荧光定量PCR检测细胞IL-8、 IL-6、 IL-1β、肿瘤坏死因子α(TNF-α)的mRNA水平, ELISA检测细胞培养上清液IL-8蛋白水平,流式细胞术检测THP-1细胞的凋亡, Western blot法检测细胞STAT3、细胞外信号调节激酶(ERK)的蛋白磷酸化水平;采用(0、 1、 5、 10)μmol/L的ERK通路选择性抑制剂U0126预处理THP-1细胞,反转录PCR检测U0126对Stattic诱导THP-1细胞表达IL-8 mRNA水平的影响。结果 (10～20)μmol/LStattic显著上调IL-8在THP-1细胞中的mRNA和蛋白表达,仅(15、 20)μmol/LStattic能诱导THP-1细胞凋亡; Stattic处理THP-1细胞1、 3、 6、 12、 24 h,均显著上调IL-8的mRNA水平,以3 h时最为明显,在6 h以后呈时间依赖性上调IL-8的蛋白水平并诱导THP-1细胞凋亡;Stattic呈浓度和时间依赖性抑制STAT3磷酸化,时间依赖性地诱导ERK磷酸化,在(1、 5、 10、 15、 20)μmol/L时均显著诱导ERK磷酸化。另外, U0126显著抑制Stattic诱导的IL-8 mRNA表达。结论 STAT3抑制剂Stattic通过激活ERK信号通路诱导THP-1细胞凋亡和IL-8产生。     

不同类型乳腺组织中CD44~+/CD24~-细胞的数量与分布

目的检测CD44+/CD24-细胞在乳腺正常组织及良恶性肿瘤中的数量与分布特点,探讨其在乳腺癌发生、发展中的作用。方法采用免疫组化SP双染法,检测了30例乳腺正常组织(normal tissue,NT),30例乳腺纤维腺瘤(fibroadenoma,FA),60例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)中的CD44及CD24的共表达情况。结果在乳腺NT及FA中,可见CD44+/CD24+,CD44+/CD24-,CD44-/CD24-3种表型,而在IDC中,除上述3种表型外,尚可见CD44-/CD24+表型。从NT,FA到IDC,CD44+/CD24-细胞的阴性率(-,阳性率1%)依次降低(40.0%→36.7%→35.0%);而强阳性率(,阳性率60%)依次升高(0.0→6.7%→21.7%)。结论 CD44+/CD24-可能作为一种阶段性祖细胞标记,参与了正常乳腺的分化及乳腺肿瘤的发展过程。     

在乳腺癌干细胞中Hedgehog信号通路相关基因表达增强

目的 了解Hedgehog信号通路在乳腺癌发生发展中的作用.方法 用免疫磁珠法从无血清培养的乳腺癌悬浮细胞中分选CD44+CD24-细胞和非CD44+CD24-细胞,用real-time RT-PCR法检测Hedgehog信号通路主要分子$HH、PTCH1、SMO和GLI1 mRNA在细胞中的表达,用免疫组织化学法检测上述因子在乳腺癌组织中的表达.结果 分选出的CD44+CIDA-细胞约占乳腺癌悬浮细胞总数的8.25%,分选出的CD44+CD24-细胞表达干细胞标志蛋白ALDHA1和Oct-4;SHH、PTCH1、SMO和GLI1 mRNA在CD44+CD24-细胞中的表达均高于其在非CD44+CD24-细胞中的表达(P＜0.05);SMO和GLI1蛋白在三阴性乳腺癌的表达均高于非三阴性乳腺癌组织(P＜0.05).结论 在乳腺癌干细胞CD44+CD24-细胞中Hedgehog信号通路被激活,抑制癌症干细胞中Hedgehog通路的活化可能会降低或阻止乳腺癌的复发及化疗耐受.     

盐霉素通过TGFβ1/Smad信号通路抑制MMP-2、9降低CD44~+/CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力

目的分析盐霉素对CD44~+ /CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力的影响,并初步探讨其影响机制。方法通过有血清和无血清培养技术培养人乳腺癌MCF-7细胞株,收集两种细胞,对其CD24、CD44标志物进行荧光染色,采用流式细胞仪检测CD44~+ /CD24~(-/low)亚群细胞的比例;盐霉素培养MCF-7细胞株和CD44~+ /CD24~(-/low)表型乳腺癌干细胞,MTT法筛选出引起CD44~+ /CD24~(-/low)表型乳腺癌干细胞细胞凋亡低于IC50的浓度;Transwell技术检测MCF-7和CD44~+ /CD24~(-/low)表型乳腺癌干细胞的迁移和侵袭能力,以筛选出的浓度诱导CD44~+ /CD24~(-/low)表型乳腺癌干细胞,以排除盐霉素对该细胞增殖抑制作用的影响,Transwell技术检测该细胞迁移和侵袭能力的变化;Western blot技术检测TGFβ1、Smad2、Smad3、p-Smad2、pSmad3、MMP-2、MMP-9蛋白水平的变化。结果 CD44~+ /CD24~(-/low)表型乳腺癌干细胞在无血清培养和有血清培养中的比例分别为(86.93±0.53)%和(19.98±0.62)%(P0.01),CD44~+ /CD24~+ 表型细胞的比例分别是(12.68±0.59)%和(79.90±0.57)%(P0.01);MTT法筛选出低于IC50的浓度是1、3、5、7μmol/L;Transwell技术检测CD44~+ /CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力明显高于MCF-7细胞株,并随盐霉素浓度的上升呈下降趋势(P0.05)。Western blot技术检测TGFβ1、Smad2、Smad3、p-Smad2、p-Smad3、MMP-2、MMP-9蛋白水平下调(P0.01)。结论盐霉素可能通过TGFβ1/Smad信号通路下调MMP-2、MMP-9蛋白水平,从而降低CD44~+ /CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力。     

人鼻咽癌细胞株分选CD133~+细胞实验研究

目的观察CD133在人鼻咽癌细胞株中的表达,探讨CD133+肿瘤细胞的体外增殖及分化能力从而确定鼻咽癌肿瘤干细胞的标志。方法使用免疫细胞化学及流式细胞技术检测鼻咽癌CNE2Z细胞株中的表达,免疫磁珠分选技术纯化肿瘤细胞,体外培养,观察其增殖及分化能力。结果鼻咽癌CNE2Z细胞株中有0.168%呈微量阳性表达,利用免疫磁珠分选技术纯化细胞的百分比为87.2%,免疫磁珠富集的CD133+肿瘤细胞在无血清培养基中1、3、5、7天的吸光度均高于相同条件下未分选细胞和CD133-细胞;CD133+在培养体系中的比例逐日下降,至培养的第12天,由第1天的87.2%下降至0.1%。结论鼻咽癌CNE2Z细胞株中,CD133+癌细胞有比其他细胞亚群强的体外分化和增殖能力,具有自我更新、生成其他表型肿瘤细胞等干细胞样特性,CD133可能是肿瘤起始细胞的标志之一。     

Predictive value of CD44 and CD24 for prognosis and chemotherapy response in invasive breast ductal carcinoma

Objective: Cells with unique phenotypes and stem cell-like properties have been found to exist in breast cancer. The aim of the present study was to study the relationship of CD24, CD44, CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes’ with clinico-pathological features, chemotherapy response and with prognosis. Methods: The study included paraffin-embedded tissues of 140 primary and secondary invasive ductal carcinoma samples. All the patients received routine chemotherapy. Expression of CD24, CD44, ER, PR, and Her2 were assayed immunohistochemically. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low), CD44(+)/CD24 (+), CD44(-)/CD24(-) and CD44(-)/CD24(+) cells. The association between the proportions of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) and clinicopathological features, chemotherapy response and with prognosis of these patients was evaluated. Results: CD24 expression was not significantly associated with tumor characteristics, but was significantly associated with poor prognostic variables including ER-, PR-, HER2(+) and triple negative (TN) phenotype; There was no association of CD44 with nodal status, age or HER2 expression. In the correlation analysis, CD24 expression was positively associated with chemotherapy response (P = 0.018), however, CD44 expression was not associated with pathological response to chemotherapy When both markers are considered, the CD44(+)/CD24(-) phenotype had the poor prognosis. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement, recurrent or metastatic tumors and ER/PR status. High CD44(+)/CD24(-) phenotype had poor response to chemotherapy. The median disease-free survival (DFS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 19.8 ± 2.6 months and 31.7 ± 4.2 months, and the median overall survival (OS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 33.5 ± 2.8 months and 51.4 ± 3.9 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44(+)/CD24(-/low) tumor cells was strongly correlated with DFS and OS. However, the CD44(-)/CD24(+), CD44(+)/CD24(+), CD44(-)/CD24 (-) phenotype had no relation with prognosis. Conclusion: There was significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor metastasis, prognosis and chemotherapy response. The CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.     

恶性肿瘤干细胞标记物CD34在鼻咽癌细胞系的表达

BACKGROUND:Previous research have confirmed that CD34 is closely related to oncogenesis, progress, recurrence, metastasis and drug-resistance of various cancers, but its role in nasopharyngeal carcinoma remains unclear. OBJECTIVE:To sort cells positive and negative for CD34 in nasopharyngeal carcinoma cell lines and to detect cell proliferation and migration. METHODS:Expressions of CD34 in nasopharyngeal carcinoma cell lines 5-8F, 6-10B, CNE1 and CNE2 were detected by flow cytometry. And CD34+ and CD34^- cells were sorted based on cell surface markers for purity identification. Afterwards, proliferation and migration of CD34⁺ and CD34^- cells were detected by MTT assay, colony-formation assay and scratch assay. RESULTS AND CONCLUSION:All four nasopharyngeal carcinoma cell lines expressed CD34 in 0.1%-0.2%, and the level of CD34 was closely related to the cell growth density. The purity of CD34⁺ cell was more than 98% in the sorted CD34⁺ cell populations, but no CD34⁺ cells were found in the sorted CD34^- cell populations. At 1, 3, 5 and 7 days the proliferation rate of CD34⁺ cell, populations was significantly higher than that of CD34^- cells (P < 0.05). Consistently, the colony-formation efficiency of CD34⁺ cell was significantly higher than that of CD34^- cells (P < 0.05). Moreover, CD34⁺ cells migrated significantly faster than CD34^- cells by scratch assay (P < 0.05). In conclusion, CD34⁺ cells cultured in vitro display higher proliferation and migration capacities, indicating that CD34⁺ cells have the potential of nasopharyngeal carcinoma stem cells.     

The clinicopathological significance of CD44+/CD24-/low and CD24+ tumor cells in invasive micropapillary carcinoma of the breast

Breast cancer cells with a CD44(+)/CD24(-/low) phenotype have been suggested to have tumor-initiating properties. It is unclear whether their presence correlates with clinicopathological features of invasive micropapillary carcinoma (IMPC) of the breast, an unusual subtype of breast cancer with a high incidence of lymph node metastasis and poor prognosis. CD44 and CD24 expression was determined by double-staining immunohistochemistry in 103 cases of IMPC and in 94 cases of invasive ductal carcinoma (IDC). The prevalence of CD44(+)/CD24(-/low) tumor cells was higher in IMPC than in invasive ductal carcinoma IDC (P=0.018). The CD44(+)/CD24(-/low) tumor cells were also detected in adjacent stroma surrounding the micropapillary structure in 53.4% (55/103) of IMPC, but only in 7.4% (7/94) of stroma of IDC. These tumor cells in stroma of IMPC were positive for vimentin and α-smooth muscle actin, and negative for E-cadherin. The CD44(+)/CD24(-/low) tumor cells in the micropapillary structure of IMPC were associated with those in stroma (P=0.000). Moreover, they were both associated with lymphovascular invasion and extranodal extension, respectively (P<0.05). The proportion of CD24(+) tumor cells was also higher in IMPC than in IDC (P=0.035), and the CD24(+) tumor cells were associated with lymph node metastasis in IMPC (P=0.010). The results suggest that the increased proportion of CD44(+)/CD24(-/low) tumor cells and CD24(+) tumor cells and the epithelial mesenchymal transition may play an important role in aggressiveness and high metastatic risk of breast IMPC.     

CD44+CD24-/low乳腺癌干细胞活性与多药耐药的相关性

BACKGROUND:Tumor stem cells are found to be involved in the recurrence, metastasis and drug resistance of the tumor. OBJECTIVE:To explore the relationship between cell activity and multidrug resistance of CD44⁺CD24^-/low breast cancer stem cells. METHODS: CD44⁺CD24^-/low breast cancer stem cells sorted from multidrug resistant breast cancer cell line MCF-7/ADR were detected as percentage using flow cytometry. P-gp fluorescence intensity of the cell membrane and MDR mRNA expression in sorted cells and MCF-7/ADR were detected using flow cytometry and RT-PCR, respectively. RESULTS AND CONCLUSION:After sorting by flow cytometry, the proportion of CD44⁺CD24^-/low breast cancer stem cells was more than 90%, indicating that the sorted cells could meet the needs of the subsequent experiment. CD44⁺CD24^-/low cell subsets exhibited stronger ability to form microspheres than non- CD44⁺CD24^-/low cell subsets. The P-gp fluorescence intensity and MDR mRNA expression of CD44⁺CD24^-/low cells were significantly higher than those of MFC-7/ADR cell line (P < 0.05). These experimental findings suggest that CD44⁺CD24^-/low breast cancer stem cells sorted from MCF-7/ADR cell lines have a strong ability to form cell microspheres in vitro, and significantly raise the level of P-gp protein and MDR mRNA expression, which may be one of the causes of multidrug resistance.     

STAT3 mediates resistance of CD44+CD24-/low breast cancer stem cells to tamoxifen in vitro

We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro.The capacities for mammosphere formation and STAT3 expression of CD44+CD24-/low MCF-7 and MCF-7 were observed.The CD44+CD24-/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant(TAM-R) cells.Cell cycle,apoptosis,STAT3 and phospho-STAT3 changes were observed af-ter treatment with tamoxifen.Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed.CD44+CD24-/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7.The CD44+CD24-/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7.Cell cycle changes,anti-apoptotic effects and STAT3 changes were also found.Mean-while,the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen.It is concluded that STAT3 plays an essential role in breast cancer stem cells,which correlated with tamoxifen resistance.     

CD24,ALCAM在大肠癌的表达及其临床意义

目的:探讨CD24,ALCAM 在大肠癌中的表达及其与细胞增殖、血管生成的关系。方法:运用免疫组织化学检测66例大肠癌肿瘤组织CD24,ALCAM,CD34,PCNA 的表达情况,根据CD34 的染色情况计算出大肠癌组织的微血管密度（microvessel density, MVD）,根据PCNA染色情况计算出肿瘤细胞PCNA标记指数。结果：免疫组织化学染色显示正常大肠黏膜CD24,ALCAM 绝大部分呈阴性染色,超过75%的大肠癌细胞有不同程度的CD24 染色。44%的肿瘤CD24 呈中等强度表达,26%的肿瘤呈强阳性表达。 高Dukes分期、高pTNM分期及有淋巴结转移、浆膜外浸润的癌组织中CD24 蛋白染色强度显著高于对应组（P＜0.01)。68% 的大肠癌细胞有不同程度的ALCAM 染色。ALCAM 表达与浸润深度、pTNM分期,淋巴结转移明显正相关。在CD24,ALCAM 阳性表达病例中,PCNA 的表达随着CD24 表达强度的升高而升高（P＜0.05）。大肠癌CD24 蛋白表达强度与大肠癌微血管密度轻度相关（r=0.228,P=0.019）。大肠癌ALCAM 蛋白质表达与MVD无关（P=0.17）。结论：CD24,ALCAM 可能在大肠癌发生发展中起重要作用。     

WSX-1 over-expression in CD4(+) T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation

WSX-1 is a component of the IL-27R. Analyses of WSX-1 knockout (WSX-1(-/-)) mice have shown that IL-27/WSX-1 signaling is essential for the proper development of T(h)1 responses and that WSX-1 can suppress cellular activation and pro-inflammatory cytokine production. We have generated transgenic mouse lines over-expressing the WSX-1 gene under the control of the T cell-specific CD2 promoter (WSX-1 Tg mice). Unexpectedly, like activated CD4(+) T cells from WSX-1(-/-) mice, activated CD4(+) T cells from WSX-1 Tg mice showed increased proliferation, augmented IL-2 production and up-regulated surface expression of activation markers. IL-27-mediated tyrosine phosphorylation of STAT1 was also enhanced in WSX-1 Tg CD4(+) T cells, but STAT3 activation was normal. Exogenous IL-27 supported the proliferation of wild-type CD4(+) T cells but suppressed that of WSX-1 Tg cells. WSX-1 over-expression increased IFN-gamma production in T(h)1-polarized CD4(+) T cells, but also promoted T(h)2 cytokine production under T(h)1-polarizing conditions. Importantly, WSX-1 over-expression failed to suppress T(h)2 cytokine production under T(h)2-polarizing conditions. Cytokine hyperproduction was also observed in vivo in WSX-1 Tg mice injected with Con A. Our data suggest that WSX-1 plays a pivotal role in regulating T cell responsiveness to TCR stimulation and that the correct balance of STAT1/STAT3 activation downstream of IL-27R engagement is crucial for the physiological function of IL-27.