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101.
目的对子宫颈鳞癌(Cervical squamous cell carcinoma,CSCC)组织中T、B、NK淋巴细胞的浸润与肿瘤免疫状况进行研究,探讨免疫细胞的变化规律,阐明局部免疫状态对CSCC发展的影响,为CSCC的免疫治疗及预后提供理论依据和参考指标.方法用免疫组织化学(S-P)法,以CD4、CD8标记T细胞、CD20标记B细胞、CD57标记NK细胞,经计数分析和SPSS11.0统计软件处理.结果在早期CSCC组织中浸润淋巴细胞种类与数量依次为CD8+、CD20+、CD57+和CD4+,差别显著(P<0.05).在进展期CSCC组织中浸润淋巴细胞类型与数量依次为CD8+、CD20+、CD4+和CD57+,差别显著(P<0.05).4种淋巴细胞在进展期高分化CSCC中的数量,无显著差异(P>0.05);但在进展期中、低分化CSCC中的数量,均存在着显著差异(P<0.05).T淋巴细胞浸润的数量伴随分化程度的降低而增高,尤其CD8+T淋巴细胞增加更明显;CD4+/CD8+T淋巴细胞<1,且CD4+与CD8+T淋巴细胞的比例逐渐降低.结论在CSCC组织中浸润的淋巴细胞中以T细胞为主,其次为B细胞,NK细胞浸润最少,说明CSCC局部以细胞免疫为主,体液免疫也不容忽视.CD8+T细胞比例增加是细胞免疫受抑制的表现.CSCC组织中T细胞抗肿瘤免疫受到抑制,需要免疫调节,增强抗肿瘤免疫力. 相似文献
102.
Dr. Yvonne Paterson 《Immunologic research》1998,17(1-2):191-207
Our studies are mainly focused on developing strategies of immune regulation. In the case of infectious and neoplastic disease,
our approach is to upregulate cell-mediated immunity to viral of tumor antigens using an intracellular bacterium as a vector
for targeting these antigens to the major histocompatibility complex (MHC) class I and class II pathways of antigen processing,
in addition to exploiting the adjuvant properties of the vector to stimulate innate immunity. In the area of autoimmunity,
we are attempting to downregulate the immune response by specific immune intervention directed against autoreactive T cells.
In these studies we use murine models for multiple sclerosis. Our approach is to use both rationally designed T cell receptor
(TCR) peptide analogs and recombinant viral vectors that express TCR components to regulate the disease. 相似文献
103.
Federica Cavallo Alfonso Martin-Fontecha Matteo Bellone Silvia Heltai Evelina Gatti Paola Tornaghi Massimo Freschi Guido Forni Paolo Dellabona Giulia Casorati 《European journal of immunology》1995,25(5):1154-1162
Although the transfection of B7-1 cDNA into a few mouse tumor cell lines can induce anti-tumor T cell immunity, its expression alone is ineffective in many other tumor cell lines tested. We were interested to study what factors limit B7-1 co-stimulatory activity, and decided to investigate whether B7-1 requires the cooperation of ICAM-1 to provide the minimal co-stimulatory signal for establishing an efficient anti-tumor immunity. We show that the transfection of B7-1 cDNA into three ICAM-1+ (plasmocytoma J558L, T lymphomas EL-4 and RMA), but not into two ICAM-1? tumor cell lines (adenocarcinoma TS/A and melanoma B16.F1), is sufficient to induce their complete rejection in syngeneic mice. The expression of ICAM-1 is necessary for the rejection of the B7 expressing tumors, since the primary response elicited by B7-1+ EL-4 and RMA clones expressing reduced levels of ICAM-1 is severely reduced. Furthermore, super-transfection of ICAM-1 cDNA into B7-1+ adenocarcinoma and melanoma clones optimizes their primary rejection. Histologic examination of transfected tumors reveals that B7-1 and ICAM-1 exert a potent pro-inflammatory activity. The intra-tumor infiltration is composed of both eosinophils and lymphomono-cytes, and is already massive 5 days after the tumor challenge. The primary rejection of the B7-1+ ICAM-1+ tumors depends critically on CD8+ T cells, natural killer cells and granulocytes, but is independent of CD4+ T cells. Remarkably, in addition to its effects on the early phases of the immune response, the co-expression of ICAM-1 and B7-1 on tumors is also necessary for the efficient induction of a memory response. In fact, only the primary challenge with B7-1+, ICAM-1+ tumor cells protects the majority of the mice from a second injection of parental tumor cells. Collectively, our findings indicate that B7-1 and ICAM-1 are fundamental components for triggering the primary rejection of tumors and establishing a protective memory response. These findings may help to define new strategies for the rational application of co-stimulation in tumor immunotherapy. 相似文献
104.
Paterson Y 《Immunologic research》2003,27(2-3):451-462
Our laboratory is interested in the properties of proteins that render them immunogenic, and how such immunogenicity may be
modulated in vivo. We are attempting to enhance the immune response in the design of more effective vaccines against viral
diseases, such as HIV, and against tumor antigens expressed on breast, ovarian, and cervical cancer and B cell lymphomas.
Our main approach is to use a facultative intracellular bacterium, Listeria monocytogenes, which has the unusual ability to live and grow in the cytoplasm of the cell and is thus an excellent vector for targeting
passenger antigens to the major histocompatibility complex (MHC) class I pathway of antigen processing with the generation
of authentic cytotoxic T lymphocytes (CTL) epitopes. In the field of tumor immunotherapy, we are also developing nonliving
vaccine vectors for tumor antigens. 相似文献
105.
Oncogenesis is the consequence of a series of genetic alterations that allow unrestrained cellular growth, tissue invasion, and eventual metastases. Tumor-related genes can be classified into functional categories. Proto-oncogenes/oncogenes have a stimulatory role in cell growth, and the inactivation of cancer-suppressor genes/antioncogenes results in the loss of cell cycle regulation. More recently, three other groups of tumor-related genes have been recognized. They include the antiapoptosis genes which protect from programmed cell death, the antimetastasis genes, and multidrug resistance genes. Besides aiding in tumor diagnosis, the detection of such tumor-associated genes and their products allows the identification of individuals with an inherited predisposition to neoplastic growths, and the overexpression of many of these oncogene products has been shown to be a potential marker of tumor behavior and a predictor of treatment outcome and response. The ability to utilize DNA and RNA probes for nucleic acid hybridization and polymerase chain reaction procedures in cell and tissue preparations of solid tumors and lymphoid proliferations expands and complements the information provided by immunohistochemical techniques. These probes allow direct visualization and correlation of specific genes and their protein products with cytomorphologic features, and form a powerful addition to the armamentarium of the cytopathologist and surgical pathologist. © 1995 Wiley-Liss, Inc. 相似文献
106.
Pierre-Andr Bcherel Liliane Le Goff Sandra Ktorza Fateh Ouaaz Jean-Michel Mencia-Huerta Bernard Dugas Patrice Debr M. Djavad Mossalayi Michel Arock 《European journal of immunology》1995,25(10):2992-2995
Human keratinocytes (HK) generate nitric oxide (NO) and proinflammatory mediators following activation with either IgE/anti-IgE immune complexes or a combination of lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Recently, interleukin-10 (IL-10) has been shown to down-regulate various inflammatory responses and to be secreted by lymphocytes and dendritic cells during skin inflammatory reactions. We show here that IL-10 down-regulates the production of tumor necrosis factor (TNF)-α and IL-6 by activated HK. Also, induction of inducible nitric oxide synthase (iNOS) expression in HK by IgE/anti-IgE or LPS/IFN-γ is significantly reduced by the addition of IL-10. This effect is dose dependent and correlates with reduction of iNOS mRNA production and enzyme level. Therefore, IL-10 down-regulates NO-mediated HK inflammatory responses and may thus participate in the regulation of the skin immune network. 相似文献
107.
目的:探讨负性刺激分子在肿瘤细胞逃避免疫效应中的作用.方法:以L929细胞为靶细胞,体内致敏C57BL/6小鼠,注入PD-L1、PD-L2抗体阻断,并设立未致敏对照组.分离小鼠脾细胞,体外采用3H-TdR掺入法、荧光标记双染色FCM以及PI染色FCM法分别检测淋巴细胞增殖反应、活化诱导的细胞凋亡以及脾细胞及其培养上清对肿瘤细胞的杀伤效应.结果:L929细胞表达PD-L1,而不表达PD-L2.体内与体外联合应用PD-L1抗体,能显著增强L929肿瘤细胞诱导的致敏组小鼠脾细胞的增殖活性和特异性杀伤效应,并可抑制活化诱导的T细胞凋亡;PD-L1抗体亦可增加L929细胞诱导的未致敏组小鼠脾细胞的增殖活性和促进其脾细胞培养上清对L929细胞的杀伤效应.结论:PD-L1抗体可通过阻断PD1/PDL途径促进初始T细胞和致敏T细胞介导的抗瘤效应. 相似文献
108.
Lymphotoxin but not tumor necrosis factor functions to maintain splenic architecture and humoral responsiveness in adult mice 总被引:1,自引:0,他引:1
Fabienne Mackay Gerard R. Majeau Pornsri Lawton Paula S. Hochman Jeffrey L. Browning 《European journal of immunology》1997,27(8):2033-2042
To compare the function of the tumor necrosis factor (TNF) and lymphotoxin (LT)α/β systems in the mature immune system, these two pathways were blocked with soluble receptor-immunoglobulin (R-Ig) fusion proteins in normal adult mice. Inhibition of LTα/β signaling using LTβR-Ig or a blocking monoclonal antibody against murine LTβ had profound effects. The spleen lacked discrete B cell follicles and the marginal zone was altered. Less marked changes were detected in lymph nodes. LTα/β inhibition also prevented germinal center formation in the spleen and impaired Ig production in response to sheep red blood cells (SRBC) immunization. These results show that the LTα/β system is required for the maintenance of splenic architecture and normal immune responses, and not simply for the development of peripheral immune organs during ontogeny. In contrast, inhibition of the TNF/LTα pathway with TNF-R55-Ig did not affect the splenic architecture or the anti-SRBC response. Splenic defects and impaired antibody responses are seen in TNF-deficient mice, suggesting that TNF is important during development. Therefore relative to TNF, the LT system has the dominant influence on splenic organization and anti-SRBC Ig formation in the adult mouse. 相似文献
109.
人肿瘤细胞TH2类细胞因子的逆转与NK抗性变化的研究 总被引:3,自引:0,他引:3
目的研究促使人肿瘤细胞中TH2类细胞因子表达向TH0型的逆转及逆转后的肿瘤细胞对NK抗性的变化。方法首先用MTT方法对悬浮培养的肿瘤细胞株DB大淋巴细胞瘤、Karpas淋巴瘤、Michael淋巴瘤、Raji、HL60和K562进行了NK杀伤敏感性的筛选。选择NK不敏感的Karpas淋巴瘤和HL60,用rhIFNγ、rhIL-12和抗IL-10McAb经不同组合对其进行由TH2类细胞因子表达向TH1类细胞因子表达的促逆转研究,并观察促逆转后的肿瘤细胞对NK抗性的变化。结果RT-PCR结果表明,经上述不同细胞因子组合诱导后,Karpas淋巴瘤细胞均从表达TH2类细胞因子为主向TH0型逆转,并且各组逆转后的肿瘤细胞对NK的抗性均有不同程度的减弱。结论TH1类细胞因子(如IFNγ)、TH2类细胞因子拮抗剂(如IL-10单抗)和IL-12不同程度地促进肿瘤细胞表达的细胞因子由TH2型向TH0/TH1型逆转。促逆转后可以改善肿瘤细胞对机体杀伤作用的敏感性,提高抗肿瘤免疫能力 相似文献
110.
利用纳米电化学传感技术进行癌症的早期检测是将来生物医学领域的一个重要发展方向.简要介绍了肿瘤早期检测用标志物的概念和电化学检测这些标志物的原理,对纳米粒子应用于电化学癌症早期检测技术的研究进展进行了详细的评述,最后对该领域的应用前景进行了展望. 相似文献