鼻咽癌组织与外周血CD4+CD25+调节性T细胞检测及临床意义

 目的 通过检测鼻咽癌患者肿瘤组织及外周血中CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞的频数,寻找客观、全面评价鼻咽癌患者免疫状态的临床指标。方法 采用流式细胞术检测40例初诊鼻咽癌患者及10例正常对照鼻咽部组织和外周血CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞比例。结果 鼻咽癌患者CD4⁺T细胞比例及CD4⁺/ CD8⁺T比值均低于对照组（P<0.05）,而CD8⁺T细胞两组间差异无统计学意义（P>0.05）,但是CD4⁺/ CD8⁺T比值在鼻咽癌组织与外周血间差异无统计学意义（P>0.05）。鼻咽癌组织及外周血中CD4⁺CD25⁺T细胞比例都高于对照组（P<0.05）,同时癌组织中该细胞比例远远高于外周血（P<0.05）。在鼻咽癌组织中CD4⁺CD25⁺T细胞与CD8+ T细胞、CD4⁺CD25^-T细胞呈负相关（r分别为-0.70、-0.675,P<0.05）,而在外周血中没有相关关系（P>0.05）。在不同T(原发肿瘤大小)组间,T4组的鼻咽癌组织中CD4⁺CD25⁺T细胞分别高于T1、T2、T3各组（P<0.05）,而在T1、T2、T3各组间差异无统计学意义（P>0.05）;鼻咽癌中CD4⁺CD25⁺T细胞比例与患者有无淋巴结转移并无关系（P>0.05）;鼻咽癌组织中Ⅲ+Ⅳ期组CD4⁺CD25⁺T细胞比例高于Ⅰ+Ⅱ期组（P<0.05）,而在外周血中两组间差异无统计学意义（P>0.05）。结论 CD4⁺CD25⁺T细胞与鼻咽癌病程进展无相关性,但是联合检测患者肿瘤组织及外周血中CD4⁺CD25⁺T细胞的频数并结合既往CD4⁺/ CD8⁺T比值会全面反应患者免疫状态,为临床治疗提供依据。     

肝癌微环境中CD4+CD25+Treg细胞与肿瘤免疫细胞的关系

[目的]探讨肝癌微环境中Treg细胞的数量增多与HCC临床分期晚的可能原因。[方法]双重酶标免疫组织化学方法检测52例HCC组织中CD4^＋CD25＋Treg细胞以及CD4^＋CD25-T（CD4^＋T）细胞分布，免疫组化EnVision法检测20例HCC组织中CD8＋T细胞分布。[结果]正常肝脏组织中未发现Treg细胞。HCC组织中Treg细胞数量较癌旁组织明显增多（P=0．000），且肝癌组织中Treg细胞的数量与其浸润性CD4＋T淋巴细胞的数量以及CD4＋T/CD8^＋T比值呈显著负相关（r=-0．539，P=0．014；r=-0．545，P=0．000），而与浸润性CD8^＋T淋巴细胞的数量无明显相关性（f=-0．403，P=0．078）。[结论]Treg细胞在体内可能通过细胞接触的方式抑制CD8^＋T淋巴细胞的增殖来抑制肿瘤局部的免疫，去除或减少HCC微环境中浸润件Tree细胞数量可能提高肿瘤局部免疫治疗效果。     

CD44+/CD24-表型与BRCA1及basal-like乳腺癌的相关性

 目的：探讨CD44⁺/CD24^-表型与BRCA1及basal-like乳腺癌的相关性。方法：收集经病理诊断为乳腺癌患者的手术切除石蜡标本共217例,根据免疫学标志物把217例乳腺癌划分为5类分子亚型：basal-like型、luminal A型、luminal B 型、Her2过表达型和normal breast-like型。应用免疫组织化学检测CK5/6、BRCA1和CD44/CD24双染的情况,分析CD44⁺/CD24^-表型与basal-like乳腺癌及BRCA1相关性乳腺癌的关系。结果：217例乳腺癌标本例中,luminal A型130例、luminal B型15例、HER2过表达型21例、basal-like型29例、Normal breast-like型22例。BRCA1相关性乳腺癌57例。basal-like乳腺癌组织中BRCA1缺失率86%（25/29）,明显高于乳腺癌其他分子亚型(P<0.001)。basal-like乳腺癌组织中含CD44⁺/CD24^-肿瘤细胞者20例 (20/29,69%),明显高于乳腺癌其他分子亚型(P=0.003);BRCA1相关性乳腺癌中含CD44⁺/CD24^- 肿瘤细胞者53例(53/57,93%)。结论：BRCA1基因突变与basal-like乳腺癌有关;CD44⁺/CD24^-干细胞表型主要存在于basal-like乳腺癌及BRCA1相关性乳腺癌中。     

CD4+CD25+调节性T细胞在肿瘤免疫领域的研究进展

CD4^ CD25^ 调节性T细胞(Regulatory T cell，Treg)在维持自身免疫耐受中起重要作用。本文就其在肿瘤免疫领域的研究进展进行综述。     

CD4+CD25+调节性T细胞及其在肿瘤免疫治疗中的意义

CD4^＋ CD25^＋调节性T细胞是具有独特免疫调节功能的T细胞亚群。近年来研究发现各种恶性肿瘤患者外周血及肿瘤环境中该细胞比例增加，去除CD4^＋ CD25^＋调节性T细胞或封闭其抑制功能可以增强抗肿瘤免疫反应。CD4^＋ CD25^＋调节性T细胞成为肿瘤免疫治疗的新靶点。     

肝癌微环境中CD4~+CD25~+调节性T细胞与T细胞免疫的关系

目的:探讨肝细胞癌组织中CD4 CD25 调节性T细胞(CD4 CD25 regulartory Tcell,Treg)与肿瘤微环境T细胞免疫的关系。方法:对52例肝细胞癌组织和癌旁组织用CD4、CD25双重酶标免疫组化染色和用CD8 EnVision法染色,对癌组织中Treg细胞和CD4 T、CD8 T、CD4 T/CD8 T比值进行相关性分析。结果:正常肝脏组织中未发现Treg细胞,肝癌和癌旁组织中Treg细胞单个高倍视野平均数分别为(7.6±2.84)、(5.2±1.67),两组比较有显著差异(P<0.01);肝癌及癌旁组织中CD4 T细胞单个高倍视野平均数分别为(18.2±3.57)、(25.9±3.36),两组比较有显著差异(P<0.01);肝癌及癌旁组织中CD8 T细胞单个高倍视野平均数分别为(49.9±6.61)、(49.5±6.43),两组比较无明显差异;肝癌及癌旁组织中CD4 T/CD8 T比值分别为(0.37±0.08)、(0.53±0.09),两组比较有显著差异(P<0.01);肝癌组织中Treg细胞的数量与其浸润性CD4 T淋巴细胞的数量及CD4 T/CD8 T比值呈显著负相关(P<0.01),而与浸润性CD8 T淋巴细胞的数量分布无明显相关性。结论∶Treg细胞在肝癌微环境中可能通过抑制CD4 T淋巴细胞的增殖来抑制肿瘤局部免疫。     

肝癌微环境中CD4+CD25+调节性T细胞与T细胞免疫的关系

目的: 探讨肝细胞癌组织中CD4+CD25+调节性T细胞(CD4+CD25+regulartory T cell,Treg)与肿瘤微环境T细胞免疫的关系。方法: 对52例肝细胞癌组织和癌旁组织用CD4、CD25双重酶标免疫组化染色和用CD8 EnVision法染色，对癌组织中Treg细胞和CD4+T、CD8+T、CD4+T/CD8     

CD4＋CD25＋Foxp3＋Treg细胞调控肿瘤免疫抑制微环境的研究进展

目的： CD4＋CD25＋Foxp3＋调节性T细胞（ Treg ）是肿瘤免疫抑制微环境的主要组成部分,其在肿瘤的免疫抑制微环境中分泌IL－10、IL－35、TGF－β1和FGL2等细胞因子发挥免疫抑制作用。Treg细胞抑制CD4＋T、CD8＋T淋巴细胞和NK细胞,进而抑制特异性抗肿瘤免疫反应使肿瘤细胞更容易逃避免疫监视。进一步研究Treg细胞在肿瘤免疫中的作用机制,对深入了解恶性肿瘤的发病机制及免疫治疗具有重要的理论意义。此外,Treg细胞及其分泌的细胞因子在肿瘤治疗和预后评估等方面也具有广阔的临床应用前景。     

CD4+CD25+调节性T细胞与CD4+T、CD8+T细胞在结直肠癌组织中的分布

 目的 分析CD4+CD25+ FOXP3+调节性T细胞（Treg）与CD4+T、CD8+T在结直肠癌（colorectal carcinoma, CRC）组织中的分布及其与临床病理特征之间的关系。方法 收集42例CRC新鲜手术标本,应用冰冻切片、免疫组织化学SP法检测肿瘤组织和癌旁组织中FOXP3+、CD4+T和CD8+T阳性细胞数。结果 CRC患者肿瘤组织中FOXP3表达水平显著升高,与癌旁组织相比差异有统计学意义（P<0.01）;中低分化组Treg细胞数明显高于高分化组（P<0.01）;淋巴结转移组Treg细胞数明显高于无淋巴结转移组（P<0.05）;癌巢内CD4+、CD8+T细胞数及CD4+/CD8+值显著低于间质（P<0.01）;Ⅲ+Ⅳ期、淋巴结转移组癌巢内CD4+/CD8+比值显著低于Ⅰ+Ⅱ期及无淋巴结转移组（P<0.05）;CRC中Treg数量与癌巢内CD4+/CD8+比值显著负相关（r=-0.605, P<0.01）。结论 CRC的发生发展可能与其癌组织局部微环境中Treg数量变化相关,肿瘤局部Treg数量的增多与T淋巴细胞亚群比例失调可能成为肿瘤免疫逃逸的机制之一。     

CD4＋CD25＋调节性T细胞在血液病中的研究进展

CD4＋ CD25＋调节性T细胞是一类产生于胸腺,具有免疫无能性及免疫抑制性的细胞.以往的研究在再生障碍性贫血、白血病、特发性血小板减少性紫癜、非霍奇金淋巴瘤、骨髓增生异常综合征中进行了CD4＋ CD25＋T细胞、CD4＋ CD25hiT细胞、CD4＋ CD25＋ Foxp3、CD4＋ CD127等调节性T细胞相关抗体的测定,得出了调节性T细胞在自身免疫性血液病中减少、在肿瘤性疾病中增多的结论 .调节性T细胞在治疗自身免疫性疾病、变态反应性疾病、移植排斥、肿瘤及特异性疫苗接种方面具有巨大前景.     

外周血CD3+、CD4+、CD8+、CD19+水平与喉癌患者预后的相关性

目的 探讨喉癌患者免疫水平的变化与病情进展的关系.方法 选取56例喉癌患者,用流式细胞仪检测不同分组的喉癌患者外周血淋巴细胞和NK细胞的表达水平.结果 手术后患者CD19+显著性下降(P＜0.05),而NK细胞显著上升(P＜0.05);有淋巴结转移的患者比无淋巴结转移的患者NK细胞上升,CD4+下降,二者均有统计学差异(P＜0.05);病理分期中Ⅲ～Ⅳ期的患者比Ⅰ～Ⅱ期表现出CD19+显著性下降(P＜0.05),CD4+则显著上升(P＜0.05).在术后随访18个月中,有复发或转移的患者比无转移且无复发患者CD4+下降,而NK细胞和CD19+上升,均具有统计学差异(P＜0.05).结论 喉癌患者免疫状态和病情之间有一定的联系.     

Epithelial mesenchymal transition correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer

The epithelial-mesenchymal transition (EMT) has been linked to induction of a stem-cell like phenotype, characterized by altered cell surface marker expression and increased tumor formation. The aim of this study was to investigate whether EMT correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer. The morphology of untreated and gemcitabine-treated SW1990 gemcitabine-resistant cells and normal SW1990 cells were compared. NF-κB p65 expression was knocked down using siRNA. Vimentin and E-cadherin expression were analyzed using western blotting, and CD24+CD44+, CD133+ cells were quantified by FACS. Additionally, immunohistochemistry of EMT-associated markers and stem cell-associated markers were performed in 41 cases of human pancreatic ductal adenocarcinoma. In SW1990 gemcitabine-resistant cells, gemcitabine induced a mesenchymal cell phenotype, expression of EMT-related molecular markers and increased CD24+CD44+ and CD133+ cells compared to untreated SW1990 gemcitabine-resistant and SW1990 cells. Knockdown of NF-κB p65 inhibited the ability of gemcitabine to increase the proportion of CD24+CD44+ or CD133+ cells and expression of EMT-related molecular markers. In human pancreatic ductal adenocarcinoma, significant correlations were observed between expression of the EMT-associated markers vimentin and E-cadherin, and stem cell-associated markers CD24, CD133 and CD44. This study demonstrated that EMT correlated with CD24+CD44+ and CD133+ cells in pancreatic cancer. This study also suggests that EMT may induce cancer stem-like cells in pancreatic cancer, with different degrees of EMT probability inducing different proportions of CD24+CD44+ and CD133+ cells.     

Immune surveillance: both CD3+ CD4+ and CD3+ CD8+ T cells control in vivo growth of P815 mastocytoma.

The aim of this study was to examine whether a spontaneous immune response controls neoplastic growth in P815-bearing DBA/2 mice, and to characterize the cells involved in tumor resistance in vivo. Several cell lineages such as T-cell-receptor (TcR)-bearing T cells, NK cells and macrophages mediate some anti-tumor activity in vitro. P815 was chosen as a model because it is weakly immunogenic and is a good target both for tumor-specific, MHC-restricted CTL-mediated lysis and for MHC-unrestricted lysis exerted by long-term cultured lymphocytes or activated macrophages. Since most "NK-like activity" in freshly isolated populations appears to be associated with CD3- cells, whereas antigen-specific, MHC-restricted T cells mostly express CD3 determinants, CD3 was a good marker for evaluating the role of T cells and "NK" cells in tumor resistance in vivo. The survival of anti-CD3-treated animals that were inoculated with tumor cells was strongly reduced (mean survival time: 17 days vs. 40 days for the control group) and was associated with increased tumor growth rate. We followed the same approach to define the T-cell subset(s) that mediate(s) this immune response. Both CD4+ and CD8+ T cells were required for induction of immune control on neoplastic growth. The approach used has revealed the important role of CD4+ T cells in immune responses that control in vivo growth of a class-I-positive, class-II-negative tumor and suggests that these cells may play a central role in tumor resistance. Since CD4+ cells are activated by soluble, exogenous proteins, this finding may have important implications for immunotherapy.     

CD+4CD+25调节性T细胞与肿瘤免疫

 近期研究发现一个有独特免疫调节功能的T细胞亚群：CD+4 CD+25调节性T细胞,不仅能抑制自身免疫性疾病发生,还参与肿瘤免疫的调节。这群细胞具有免疫无能和免疫抑制特性,与肿瘤免疫逃逸有密切的关系。肿瘤环境中CD+4 CD+25调节性T细胞增加,导致肿瘤免疫失调,去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供了一种新的思路。     

CD4^＋CD25^＋调节性T细胞与肿瘤的相关性研究

通过了解CD4^＋CD25^＋调节性T细胞（CD4^＋CD25^＋Treg）表面分子的特性和CD4^＋CD25^＋Treg在外周血和组织中的表达,认识CD4^＋CD25^＋Treg在肿瘤免疫调节中的作用,探索其作用的分子机制。     

The impact of CD4+CD25+ Treg on tumor specific CD8+ T cell cytotoxicity and cancer

There is sufficient evidence to suggest that tumor growth elicits specific immune responses, including CD8(+) and CD4(+) T cell responses that may delay tumor growth and could potentially be harnessed to eradicate cancer. Nevertheless the frequent outcome of cancer is lethality associated with uncontrolled growth and dissemination of tumor cells. The failure of the immune response may be naturally programmed and related to a specific subpopulation of CD4(+)CD25(+) regulatory T cells, whose function is to protect us against autoimmunity. Recent investigations have shed light on the in vivo behavior and functions of these cells. It is becoming evident that a major impact of these cells is on the cytolytic action of specific CD8(+) T cells that target the tumor. Inhibition of cytotoxicity is dependent on TGF-beta signaling by the effector cells. Thus, targeting immune regulation may provide a promising approach to the immune therapy of cancer. This approach however could also have unexpected deleterious consequences, as surprising new observations indicate that regulatory T cells can also delay tumor growth by independent mechanisms that relate to their cross talk with the innate immune response to cancer.     

Co-immunization with L-Myc enhances CD8+ or CD103+ DCs mediated tumor-specific multi-functional CD8+ T cell responses

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c⁺ DCs, CD8⁺CD11c⁺ DCs and CD103⁺CD11c⁺ DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8⁺ T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8⁺ T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8⁺ T cells or CD8⁺CD11c⁺ DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8⁺ DCs and CD103⁺ DCs mediated CD8⁺ T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8⁺ T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8⁺ DCs and CD103⁺ DCs mediated tumor-specific multi-functional CD8⁺ T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.     

CD4+CD25+调节性T细胞与抗肿瘤免疫

CD4^＋CD25^＋调节性T（CD4^＋CD25^＋Tr）细胞是一类维持机体自身耐受的T细胞亚群,分布广泛,但不同组织表型有所不同。它们可由胸腺自然产生,也可在外周血中诱导产生,其活化要依赖于特异性抗原的存在。CD4^＋CD25^＋Tr细胞发挥抑制效应是通过细胞接触依赖或分泌细胞因子这两种方式。去除CD4^＋CD25^＋Tr细胞或抑制其功能,重新募集效应性T细胞能够增强机体抗肿瘤作用,这将成为一种可行的肿瘤免疫治疗方法。     

T-cell prolymphocytic leukemia with an unusual phenotype CD4+ CD8+

A patient with T-cell prolymphocytic leukemia (T-PLL) is described. The outcome was poor, with death 8 months after diagnosis, despite several therapeutic interventions. The cells carried both CD4 and CD8 epitopes, but other thymocytic markers were absent. The spleen showed infiltration of CD4+ CD8+ prolymphocytes in the red pulp and in T-cell-dependent areas of the white pulp. Immunologic function studies revealed proliferation after stimulation with mitogens and even several antigens. However, in the mixed lymphocyte culture the T-PLL cells did not proliferate. Cytotoxic T-cells could not be induced. In T-non-T recombination experiments neither helper nor suppressor cell function was found for pokeweed mitogen-dependent plasmablast generation of normal B-cells. Cytogenetically, many abnormalities were found. Among them, 14q+; absence of chromosomes 8, 11, and 22; and the presence of large marker chromosomes and fragments.