Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma

We examined cell surface expression of five B7 costimulatory molecules (B7-H1, B7-DC, B7h, CD80 and CD86) in human oral squamous cell carcinoma (SCC) lines. Most human SCC cell lines expressed various levels of B7-H1 and B7-DC. Their expression was further upregulated by interferon (IFN)-gamma stimulation. Immunohistochemical staining revealed substantial and predominant expression of B7-H1 on human primary oral SCC. A murine SCC line, NR-S1, neither expressed B7-H1 nor B7-DC, but induced B7-H1 by IFN-gamma stimulation in culture and the inoculation in vivo. Although NR-S1 tumors grew progressively in immunocompetent syngeneic mice, the administration of blocking anti-B7-Hl or anti-PD-1 mAb significantly inhibited the tumor growth, suggesting the negative regulation of host immune responses by the PD-1:B7-H1 pathway. Our results demonstrate that B7-H1 is predominantly induced on oral SCC within the B7 family molecules. A successful inhibition of tumor growth by blockade of the PD-1:B7-H1 pathway may implicate a new approach for immunotherapy of oral SCC.     

B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression.

PURPOSE: B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs. EXPERIMENTAL DESIGN: The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically. RESULTS: Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02). CONCLUSIONS: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.     

12-O-tetradecanoyl phorbol 13-acetate induces the expression of B7-DC, -H1, -H2, and -H3 in K562 cells

Induction of the B7 family molecules by 12-O-tetradecanoyl phorbol 13-acetate (TPA) has been reported, however, the mechanism by which TPA up-regulates these molecules remains poorly understood. In this study, the expression of B7-DC, -H1, -H2, and -H3 in response to TPA was markedly induced in K562 cells. TPA also induced activation of ERK, p38 mitogen-activated protein kinase (MAPK), JNK, phosphatidylinositol-3-kinase (PI-3K), or nuclear factor (NF)-kappaB. Pre-treatments with protein kinase C (PKC) inhibitors significantly inhibited TPA-induced expression of B7-DC, -H1, -H2, and -H3 mRNA as well as TPA-induced phosphorylation of ERK, p38 MAPK, JNK, and PI-3K. TPA-induced expression of B7-DC, -H1, -H2, and -H3 mRNA was abrogated by pre-treatments with inhibitors of ERK and p38 MAPK. However, inhibition of PI-3K and JNK only caused decrease of TPA-induced B7-DC mRNA and B7-H3 mRNA, respectively. TPA-induced degradation of IkappaB-alpha was markedly abrogated by treatments with PKC inhibitors, but not by treatments with inhibitors of ERK, p38 MAPK, JNK, or PI-3K. NF-kappaB inhibitors significantly attenuated the expression of B7-DC, -H1, -H2, and -H3 mRNA in response to TPA. These results suggest that TPA induces the expression of B7-DC, -H1, -H2, and -H3 mRNA in K562 cells via activation of PKC, ERK, p38 MAPK, and NF-kappaB. Distinctly, the expression of B7-DC mRNA and -H3 mRNA in response to TPA is also PI-3K- and JNK-dependent, respectively.     

Oral Squamous Carcinoma Cells Express B7-H1 and B7-DC Receptors in Vivo

B7-H1 and B7-DC ligands are members of the B7 family with important regulatory functions in cell-mediated immune response. Both receptors are ligands of the programmed death receptor PD-1. B7-H1 expression has been detected in the majority of human carcinomas in vivo. B7-H1 mediated signals are able to negatively regulate activated T cell functions and survival, and enable tumor cells to overcome host response. The aim of this study was to investigate the expression of B7-H1 and B7-DC proteins in oral squamous cell carcinomas (OSCC) in vivo. Tissues from 15 samples were cryo-sected and following histological routine staining (HE), incubated with antibodies against human B7-H1 and B7-DC. Immuno-staining of pan-cytokeratin was performed to ascertain the epithelial origin of the tissue and CK 19 to demonstrate the proliferating stage. Confocal laser scanning microscopy confirmed the presence of both B7-H1 and B7-DC in all 15 OSCC. The B7-H1 and B7-DC staining was located in areas of the tissue that were identified as cancerous lesions in the previously stained HE sections before. Staining with Pan-CK and CK19 provided evidence for the epithelial origin and the proliferating stage of the tissue. The in vivo expression of the B7-H1 and B7-DC receptors in oral squamous cell carcinomas suggest that general mechanisms for immune evasion of tumors are also found in OSCC.     

B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells

Human glioblastoma is well known for its capacity to interfere with effective antitumor immune responses. B7-H1 is the third member of the B7 family that plays important roles in tumor immune evasion. Recent studies have shown that brain tumor stem-like cells (TSCs) contribute to tumorigenesis and radioresistance. However, the relationship between B7-H1 and the clinical behavior of brain TSCs remains unclear. In the present study, we report that B7-H1 is correlated with the malignancy grade of astrocyte tumors. B7-H1 was significantly upregulated at the growing edge of the tumors. Immunostaining and flow cytometric analysis indicate that B7-H1 was expressed primarily by Ki67-negative tumor cells. In vitro, tumors cultured under medium favoring the growth of neural stem cells were able to form spheres, along with expression of neural stem/progenitor cell markers. These cells were able to differentiate into different neural lineages when cultured in differentiation medium, indicating that these cells have TSC characteristics. We also found that B7-H1 was expressed, but not exclusively on CD133-positive stem cells. Interestingly, we found that CD133-negative tumor cells also had the capacity to form brain tumors. Our data establish a correlation between the expression of the negative costimulatory molecule B7-H1 and the malignancy grade of human gliomas, suggesting that B7-H1 may be a novel tumor marker and target for therapy, although it is not expressed exclusively on brain TSCs.     

Significance of B7-H1 overexpression in kidney cancer

B7-H1 is a cell surface glycoprotein belonging to the B7 family of costimulatory molecules. Constitutive protein expression is restricted to a fraction of macrophage-lineage cells, although B7-H1 can be induced on activated T lymphocytes. In addition, some human tumor cells can acquire the ability to aberrantly express B7-H1. In vitro studies demonstrate that B7-H1, expressed by tumor cells or activated lymphocytes, impairs T-cell function and survival and enhances apoptosis of activated tumor-specific T cells. Consistent with this, in vivo monoclonal antibody blockade of B7-H1 has been shown to potentiate antitumor responses in several murine cancer models. Thus, tumor-associated B7-H1 has recently garnered much attention as a potential inhibitor of host antitumor immunity. We describe herein the published investigations looking at the role of B7-H1 in renal cell carcinoma (RCC). Clinical observations demonstrate that B7-H1 is aberrantly expressed in primary and metastatic RCC. The group from Mayo Clinic recently performed immunohistochemistry on fresh-frozen and paraffin-embedded nephrectomy specimens. All patients had clear-cell RCC, and pathologic evaluation was performed by a single urologic pathologist. Their results demonstrated that B7-H1, expressed by tumor cells or lymphocytes, is associated with aggressive pathologic features, including TNM stage, nuclear grade, tumor size, and coagulative necrosis. With a median clinical follow-up of 11 years, patients with tumor B7-H1 were at significant risk of disease progression, cancer-specific death, and overall mortality even after multivariate analyses. Five-year cancer-specific survival rates were 42% and 83% for patients with and without tumor B7-H1, respectively. The basis for these associations could relate to the recognized ability of B7-H1 to inhibit antitumor T-cell-mediated immunity. Based on the current literature, B7-H1 is an independent predictor of prognosis in RCC and represents a promising target for immune manipulation in this refractory tumor.     

Significance of B7-H1 Overexpression in Kidney Cancer

B7-H1 is a cell surface glycoprotein belonging to the B7 family of costimulatory molecules. Constitutive protein expression is restricted to a fraction of macrophage-lineage cells, although B7-H1 can be induced on activated T lymphocytes. In addition, some human tumor cells can acquire the ability to aberrantly express B7-H1. In vitro studies demonstrate that B7-H1, expressed by tumor cells or activated lymphocytes, impairs T-cell function and survival and enhances apoptosis of activated tumor-specific T cells. Consistent with this, in vivo monoclonal antibody blockade of B7-H1 has been shown to potentiate antitumor responses in several murine cancer models. Thus, tumor-associated B7-H1 has recently garnered much attention as a potential inhibitor of host antitumor immunity. We describe herein the published investigations looking at the role of B7-H1 in renal cell carcinoma (RCC). Clinical observations demonstrate that B7-H1 is aberrantly expressed in primary and metastatic RCC. The group from Mayo Clinic recently performed immunohistochemistry on fresh-frozen and paraffin-embedded nephrectomy specimens. All patients had clear-cell RCC, and pathologic evaluation was performed by a single urologic pathologist. Their results demonstrated that B7-H1, expressed by tumor cells or lymphocytes, is associated with aggressive pathologic features, including TNM stage, nuclear grade, tumor size, and coagulative necrosis. With a median clinical follow-up of 11 years, patients with tumor B7-H1 were at significant risk of disease progression, cancer-specific death, and overall mortality even after multivariate analyses. Five-year cancer-specific survival rates were 42% and 83% for patients with and without tumor B7-H1, respectively. The basis for these associations could relate to the recognized ability of B7-H1 to inhibit antitumor T-cell–mediated immunity. Based on the current literature, B7-H1 is an independent predictor of prognosis in RCC and represents a promising target for immune manipulation in this refractory tumor.     

Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis

Human glioblastoma is a highly lethal tumor that is known for its immune inhibitory capabilities. B7-homologue 1 (B7-H1), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert costimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H1 in human glioma cells in vitro and in vivo. Although lacking B7.1/2 (CD80/86), all 12 glioma cell lines constitutively expressed B7-H1 mRNA and protein. Exposure to IFN-gamma strongly enhanced B7-H1 expression. Immunohistochemical analysis of malignant glioma specimens revealed strong B7-H1 expression in all 10 samples examined, whereas no B7-H1 expression could be detected on normal brain tissues. To elucidate the functional significance of glioma cell-related B7-H1 expression, we performed coculture experiments of glioma cells with alloreactive CD4+ and CD8+ T cells. Glioma-related B7-H1 was identified as a strong inhibitor of CD4+ as well as CD8+ T-cell activation as assessed by increased cytokine production (IFN-gamma, interleukin-2, and interleukin-10) and expression levels of the T-cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (mAb 5H1). B7-H1 expression may thus significantly influence the outcome of T-cell tumor cell interactions and represents a novel mechanism by which glioma cells evade immune recognition and destruction.     

胃癌中B7-H4和B7-H3的表达及薏苡仁酯对表达的影响

目的:探讨共刺激分子B7-H4和B7-H3在胃癌中的表达,以及薏苡仁酯对这两种分子表达的影响。方法:应用免疫组织化学染色检测胃癌组织中B7-H4蛋白的表达,MTT法检测薏苡仁酯对胃癌细胞株BGC-823的生长抑制效应,RT-PCR检测胃癌组织、胃癌细胞株BGC-823中B7-H4mRNA及B7-H3mRNA的表达,Western Blot检测细胞的B7-H4蛋白及B7-H3蛋白的表达。结果:B7-H4蛋白在80例胃癌组织中有60例阳性表达,阳性率75%。B7-H4蛋白的表达与患者性别、年龄、组织类型、肿瘤大小、淋巴结转移、病理分期、浸润深度无关(P>0.05)。在20例胃癌组织中,B7-H4mRNA表达明显高于癌旁正常组织,B7-H3mRNA表达明显低于癌旁正常组织(P<0.01)。薏苡仁酯可抑制胃癌细胞株BGC-823的生长,呈时间-剂量依赖性,并下调B7-H4 mRNA及蛋白的表达,上调B7-H3mRNA及蛋白的表达(P<0.01)。结论:B7-H4和B7-H3在胃癌异常的表达,可能是肿瘤免疫逃逸的原因之一;薏苡仁酯可影响胃癌细胞B7-H4、B7-H3的表达。     

抑制性协同刺激分子B7-H4在女性常见恶性肿瘤中的研究进展

B7-H4,又称V-set域T细胞激活抑制因子-1(VTCN-1),是免疫协同刺激分子B7分子超家族的新成员,其对于T淋巴细胞介导的免疫应答起到负向调节的作用,B7-H4可抑制T细胞的增殖和细胞因子的产生。B7-H4的表达与肿瘤的发生、发展及转归有着重要的联系,近年来女性常见恶性肿瘤与B7-H4的关系也受到关注。本文将对B7-H4分子与女性常见恶性肿瘤的关系进行综述,并阐述B7-H4分子作为女性恶性肿瘤潜在诊断和治疗新靶点的进展。     

Antitumor immunity after vaccination with B lymphoma cells overexpressing a triad of costimulatory molecules

BACKGROUND: The costimulatory molecules B7-1, intercellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 (LFA-3) play pivotal roles in the activation of T cells. We investigated whether in vivo vaccination with lymphoma cells infected with a recombinant, nonreplicating fowlpox (FP) virus encoding this triad of costimulatory molecules (TRICOM) could stimulate lymphoma-specific immunity. METHODS: TRICOM-infected A20 B lymphoma cells were analyzed for expression of B7-1, ICAM-1, and LFA-3. Mice (10 per group) were vaccinated with irradiated A20 cells infected with either the TRICOM vector or the wild-type FP virus (WT-FP), challenged with live A20 tumor cells, and followed for survival. Mice with established A20 tumors were also treated with irradiated TRICOM-infected A20 cells. Survival curves were compared with the log-rank statistic. The mechanism of the antitumor effect was studied by in vivo depletion of CD4(+) and CD8(+) T cells and in vitro cytotoxicity assays. All statistical tests were two-sided. RESULTS: A20 tumor cells infected with TRICOM expressed high levels of B7-1, ICAM-1, and LFA-3. Mice vaccinated with irradiated TRICOM-infected A20 cells had prolonged survival relative to mice vaccinated with WT-FP-infected cells (80% versus 20% survival at 110 days; P<.001). In mice with established tumors, tumor growth was slower in those treated with TRICOM-infected tumor cells than in those treated with WT-FP-infected cells, and this treatment provided a survival advantage (P<.001). Depletion of CD4(+) or CD8(+) T cells reduced the antitumor immunity provided by the tumor cell-TRICOM vaccine, and lymphocytes from vaccinated mice displayed in vitro cytotoxic activity toward A20 cells. CONCLUSIONS: Increasing expression of costimulatory molecules on B lymphoma cells by infection with a recombinant FP virus encoding B7-1, ICAM-1, and LFA-3 stimulates antitumor immune responses in vivo and may provide a novel strategy for treating patients with B-cell malignancies.     

Induction of therapeutic T-cell immunity by tumor targeting with soluble recombinant B7-immunoglobulin costimulatory molecules.

Tumor targeting with immunomodulatory molecules is an attractive strategy to enhance the host's antitumor response. Expression of CD80 (B7-1) and CD86 (B7-2) costimulatory molecules in tumor cells has proven to be an efficient way to enhance their immunogenicity. Here, we studied the effects of tumor targeting with biotinylated recombinant soluble B7-1- and B7-2 immunoglobulin G molecules (bio-B7-IgG) using a pretargeting approach based on the sequential use of a biotinylated antitumor monoclonal antibody and avidin. Mouse RMA T-lymphoma cells bearing either bio-B7-1-IgG or bio-B7-2-IgG on their surface prime in vitro naive CD8+ CTLs, which are highly effective in adoptive immunotherapy, and induce therapeutic immunity when injected in tumor-bearing animals. In vivo targeting of established RMA tumors with bio-B7-IgG either cures tumor-bearing mice or significantly prolongs their survival. The antitumor response induced by targeted bio-B7-IgG depends on both CD4+ and CD8+ T cells. Moreover, tumor targeting with bio-B7-IgG in vivo is critical for both expansion in lymphoid organs and mobilization into the tumor of tumor-specific CD8+ CTLs. When targeting is performed on poorly immunogenic TS/A mammary adenocarcinoma, only bio-B7-1-IgG primes naive CTLs in vitro and cures or significantly prolongs the survival of tumor-bearing mice in vivo, confirming that the two costimulatory molecules are not redundant with this tumor. Altogether, these data suggest that tumor avidination and targeting with soluble bio-B7-IgG may represent a promising strategy to enhance the antitumor response in the host.     

Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer

Background  

Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer.     

B7-H1蛋白在人胰腺癌组织中的表达及临床意义

背景与目的：恶性肿瘤细胞表达共刺激分子B7-H1来抑制T细胞功能,逃避机体的抗肿瘤免疫反应。本研究通过检测人胰腺癌组织中B7-H1蛋白的表达,探讨其与胰腺癌患者临床病理指标及预后之间的关系。方法：采用免疫组化法检测B7-H1在40例胰腺癌组织和10例癌旁正常胰腺组织中的表达情况,用卡方检验或确切概率法分析B7-H1的表达与胰腺癌患者各临床病理指标以及生存时间的关系。结果：40例胰腺癌组织中B7-H1阳性率为45.00%（18/40）,高于癌旁正常胰腺组织（P〈0.05）;B7-H1表达与患者肿瘤分期、术前CA19-9有关（P〈0.05）。多因素Cox回归模型显示,B7-H1表达是胰腺癌患者无复发生存期、总生存期的独立危险因素。结论：人胰腺癌组织中存在B7-H1蛋白表达,B7-H1表达与胰腺癌患者的预后有关。     

协同刺激分子B7-H3在结直肠癌中表达的临床意义

目的探讨协同刺激分子B7-H3在结直肠癌中的表达与患者临床病理参数的相关性。方法收集2003年1月至2003年12月在苏州大学附属第四医院行手术切除术的结直肠癌患者组织标本98例,采用免疫组织化学方法检测结直肠癌组织中协同刺激分子B7-H3的表达,分析B7-H3分子在结直肠癌组织中的表达水平。结果 B7-H3分子在结直肠癌癌灶及间质中均高表达,与患者的年龄、性别、肿瘤分期、分化程度无相关性(P>0.05),但间质高表达B7-H3分子与患者淋巴结转移显著相关(P<0.05)。结论协同刺激分子B7-H3在结直肠癌间质中高表达与患者淋巴结转移相关,对结直肠癌患者的预后判断具有潜在的临床应用价值。     

胰腺癌组织中TRPC6、B7-H1蛋白表达与肿瘤发生发展的关系

目的探讨胰腺癌组织中瞬时受体电位阳离子通道6(TRPC6)、B7免疫球蛋白超家族成员-1(B7-H1)蛋白表达与胰腺癌发生发展的关系。方法收集手术后胰腺癌病理标本112例及其对应的癌旁组织标本,采用Western-blot技术检测2组标本中的TRPC6、B7-H1蛋白表达强度,比较不同年龄、性别、病灶大小、肿瘤分化程度、临床分期、淋巴结转移的胰腺癌病理标本中TRPC6、B7-H1蛋白表达强度差异。结果胰腺癌癌组织中的TRPC6蛋白、B7-H1蛋白表达强度均高于癌旁组织,差异具有统计学意义(P<0.05)。在淋巴结阳性转移的胰腺癌组织中的TRPC6蛋白、B7-H1蛋白表达强度均高于淋巴结阴性胰腺癌患者(P<0.05);在不同TNM分期的胰腺癌组织中,Ⅰ期、Ⅱ期、Ⅲ期胰腺癌组织中的TRPC6、B7-H1蛋白表达强度呈逐渐增强的趋势,组间差异均具有统计学意义(P<0.05)。结论胰腺癌组织中TRPC6蛋白、B7-H1蛋白表达强度均显著高于癌旁组织,并且与胰腺癌的发生及发展有一定的关系。     

IFN-gamma and b7 as costimulators of antitumor immune-responses

We transfected the mouse IFN-gamma and/or the mouse B7 (T cell costimulatory molecule) cDNAs into B16 melanoma cells to study the effects of local constitutive expression of these molecules on the tumorigenicity and immunogenicity of this aggressive tumor. Cells expressing IFN-gamma (B16.IFN-gamma), B7 (B16.B7), B7 and IFN-gamma (B16.IFN-gamma/B7), and parental cells were injected subcutaneously (s.c.) into syngeneic C57BL/6 mice to compare their in vivo growth. We report that IFN-gamma secretion significantly reduced the tumorigenicity of B16 cells. These effects were related to the direct action of secreted IFN-gamma since i) in vivo injection of antiserum to IFN-gamma accelerated tumor growth, ii) development of tumor correlated with loss of IFN-gamma production, and iii) B16.IFN-gamma cells were tumorigenic in IFN-II receptor (IFN-gamma R) knockout mice, but not in parental mice. We propose that immune mechanisms are being activated by IFN-gamma since i) immune effector cells were recruited to the injection site, ii) expression of MHC class I and class II antigens was increased on cells secreting IFN-gamma and, iii) B16.IFN-gamma tumors appeared earlier in athymic mice than in immunocompetent mice. Since the in vivo growth of B16.IFN-gamma cells was not completely abolished, we studied the effect of co-expression of IFN-gamma and the T cell costimulatory molecule B7 on the tumorigenicity of B16 cells. We report that B16.IFN-gamma/B7 cells, which also express increased levels of MHC class I and class II molecules as compared to parental cells, had a dramatically suppressed tumorigenicity, while B16 cells expressing the B7 molecule only (B16.B7) were as tumorigenic as the parental cells. B16.IFN-gamma/B7 cells induced specific immune responses since all of the protected mice were able to reject challenges with parental cells. Results indicate that co-expression of two molecules which are involved in the activation of immune responses and in antigen presentation can influence the ability of the immune system to recognize and eliminate both transfected as well as parental tumor cell inocula and suggest that vaccines consisting of such cells may be used for the immunotherapy of cancer.     

B7-H4在宫颈癌组织中的表达及与临床病理特征的关系

目的:检测免疫共刺激分子B7-H4在不同宫颈组织中的表达,研究其异常表达与宫颈癌患者临床病理特征的关系。方法:选择陕西省肿瘤医院病理科2014年至2018年的石蜡包埋标本162例,采用免疫组织化学方法检测20例正常宫颈、30例宫颈上皮内瘤变(CIN)和112例Ⅰ期-Ⅳ期宫颈癌组织中B7-H4的表达水平。结果:正常宫颈组织、CIN组织、宫颈癌组织中B7-H4的阳性表达率分别为0%、20.00%、47.32%,两两相比,具有显著性差异(P<0.05)。在宫颈癌组织中,B7-H4的表达与患者年龄、病理分级无明显相关性,而随着临床期别的升高、肿瘤体积的增大、浸润深度的加深、脉管瘤栓及淋巴结转移的发生,宫颈癌组织中B7-H4的阳性表达率升高。化疗前宫颈癌组织中B7-H4阳性表达率明显高于化疗后(P<0.05)。结论:负性免疫共刺激分子B7-H4在宫颈癌的发生、进展中起到了重要作用,其作用可能为宫颈癌细胞逃逸机体免疫的机制之一。检测或干预宫颈癌组织中的B7-H4表达,可能对预测宫颈癌的发生、发展及免疫治疗具有重要意义。     

胶质瘤干细胞、肿瘤相关巨噬细胞和B7-H1在脑胶质瘤组织中的表达及其意义

目的:探讨胶质瘤干细胞（glioma stem cells,GSCs）、肿瘤相关巨噬细胞（tumor-associated macrophages,TAMs）和负性共刺激分子B7-H1(B7 homolog 1)在不同病理级别脑胶质瘤组织中的表达及其相关性。方法:对30例低级别脑胶质瘤（WHOⅠ级、Ⅱ级）和30例高级别脑胶质瘤（WHOⅢ级、Ⅳ级）标本做连续石蜡包埋切片,用免疫组化SP法检测各组标本中GSCs、TAMs和B7-H1的表达情况,采用CD133作为GSCs的标志物,以CD68作为TAMs的标志物。用Image-Pro Plus 6.0软件分析每个视野阳性染色的积分光密度（IOD）,每个组织切片在400倍镜下分析20个视野。结果:CD133、CD68和B7-H1在高级别脑胶质瘤组织中的表达水平明显高于低级别脑胶质瘤组织（P＜0.01、P＜0.01、P＜0.01）;脑胶质瘤组织中B7-H1的空间表达位置在CD68+TAMs的分布区域较强;CD133与CD68的表达呈正相关（P＜0.001）,CD133与B7-H1的表达呈正相关（P＜0.001）。结论:随着病理级别的增高,脑胶质瘤组织中GSCs、TAMs和B7-H1的表达均增高,并且CD133与CD68和B7-H1的表达呈显著正相关。