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Q3 Medicine Ejc Supplements Pub Date : 2015-11-01 DOI:10.1016/j.ejcsup.2015.08.031
T. Gening, T. Abakumova, D. Dolgova, S. Gening, I. Antoneeva
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引用次数: 0

摘要

肿瘤相关中性粒细胞(TANs)是与外周血细胞在形态功能特征上不同的细胞群(Gregory和Houghton, 2011)。2006年发表了第一项确定TANs存在为独立的不良预后因素并将TANs纳入预后风险模型的研究(Donskov, 2006)。癌症进展过程中的特定信号已被证明可诱导嗜中性粒细胞(PMN)的促肿瘤表型的出现。Frinlender(2013)指出了TANs的抗肿瘤表型。特别感兴趣的是中性粒细胞与T细胞相互作用的研究,因为后者被认为是介导抗肿瘤免疫的细胞毒性细胞。本研究的目的是评估卵巢癌淋巴样细胞浸润(LCI)和TANs的功能状态。采用免疫组织化学方法评估LCI,细胞化学方法评估卵巢癌手术切除标本中mieloproxydase (MPO)和阳离子蛋白(CP)的水平。结果以平均细胞化学系数(MCC)表示。硝基蓝四氮唑(NBT)试验强度以百分数表示。所得结果用非参数统计方法进行分析。采用Kruskal-Wallis检验评价组间差异。我们发现卵巢恶性肿瘤的典型特征是低浸润和边缘淋巴样细胞脊的形成。在肿瘤细胞快速生长的区域,即侵袭区,浸润更为密集。在某些情况下,一组肿瘤细胞从实质的主要部分分离出来,并被淋巴细胞包围。在这种情况下,癌细胞在实质中的活跃扩散与间质中淋巴样细胞的密集浸润有关。淋巴样细胞的总数和密度可以有明显的变化:从单一的淋巴样细胞均匀分散在肿瘤组织中到局灶性聚集。在肿瘤组织中,淋巴细胞的位置不规则,因此大部分浸润在基质中,在癌细胞中仅发现孤立的淋巴细胞。淋巴样细胞包括巨噬细胞(12.3±1.52%)、浆细胞(22.1±2.3%)、淋巴细胞(62.5±1.1%)和PMN(3.1±0.9%)。每1 mm2肿瘤细胞总数为224.1±32.8个。卵巢癌的淋巴细胞不形成大簇;它们与肿瘤周围基质中的其他淋巴样细胞分布在一起。浆细胞具有典型的形态结构,常位于肿瘤间质和周围。巨噬细胞是肿瘤浸润的重要组成部分。在肿瘤中,它们变得伸展和有棱角。巨噬细胞通常具有较大的尺寸,它们位于癌细胞间质和实质中。分叶性白细胞(绝大多数为中性粒细胞)常见于间质和实质的浸润中,最常见于大面积坏死的附近或中间。与外周血中性粒细胞比较,TANs功能活性分析显示MPO活性升高,分别为2.21±0.43 MCC和1.40±0.07 MCC, CP水平也升高,分别为1.51±0.39 MCC和0.83±0.43 MCC。nbt试验中TANs活性与外周血中性粒细胞无显著性差异。TANs是原发卵巢肿瘤浸润的一小部分。在卵巢癌患者中,TANs的好氧和厌氧杀菌活性指标明显超过外周血中性粒细胞。这项工作是在执行俄罗斯联邦教育和科学部第1163号-俄罗斯号国家任务的框架内进行的。
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A18

Tumor-associated neutrophils (TANs) are the cell population that differs in morphofunctional characteristics from peripheral blood cells (Gregory and Houghton, 2011). The first study to identify the presence of TANs as an independent poor prognostic factor and to include TANs into a prognostic risk model was published in 2006 (Donskov , 2006). Specific signals during cancer progression have been shown to induce the emergence of a pro-tumor phenotype of neutrophils (PMN). Frinlender (2013) points out an anti-tumor phenotype of TANs. Of particular interest is the study of interaction of neutrophils with T cells because the latter are considered to be cytotoxic cells mediating antitumor immunity. The aim of the study was to assess the lymphoid cell infiltration (LCI) and the functional status of TANs in ovarian cancer. LCI was assessed by immunohistochemistry and the levels of mieloproxydase (MPO) and cationic proteins (CP) were evaluated by cytochemical methods in ovarian carcinoma surgical resection specimens. The results were presented as a mean cytochemical coefficient (MCC). The intensity of nitroblue tetrazolium (NBT) test was expressed as a percentage. Obtained results were analyzed by nonparametric statistical methods. The Kruskal–Wallis test was used to evaluate the differences between groups.

We established that low intensity of infiltration in general and formation of marginal lymphoid cell ridge in some tumors are typical for malignant ovarian neoplasms. More intensive infiltration was found in the regions of the rapid growth of tumor cells, i.e. invasion zone. In some cases, a group of tumor cells was separated from the main part of the parenchyma and surrounded by lymphoid elements. Conditions are created under which active spread of cancer cells in the parenchyma is associated with intensive lymphoid cells infiltration in the stroma. Total count and density of lymphoid cells can significantly vary: from single lymphoid elements uniformly scattered in the tumor tissue to focal accumulations. In tumor tissue location of lymphoid cells is irregular, so most of the infiltration is in the stroma and among the cancer cells only solitary lymphocytes are found. Lymphoid cells which make up the infiltration include 12.3 ± 1.52% of macrophages, 22.1 ± 2.3% of plasma cells, 62.5 ± 1.1% of lymphocytes and 3.1 ± 0.9% of PMN. Total amount of cells was 224.1 ± 32.8 per 1 mm2 of tumor.

Lymphocytes in ovarian carcinomas do not form large clusters; they are disposed among other lymphoid cells in the stroma on the periphery of the tumor. Plasma cells have a classical morphological structure and often locate in the stroma and on the periphery of the tumor. Macrophages are an integral part of the tumor infiltrate. In the tumor they become stretched and angular. Macrophages usually have large dimensions, and they are located in the stroma as well as in the parenchyma among the cancer cells. Segmented leukocytes (presented in the vast majority by neutrophils) are constantly found in the infiltrate of the stroma and the parenchyma, most often they are found near or among massive necrosis.

Analysis of TANs functional activity in comparison with the peripheral blood neutrophils has shown that MPO activity elevated and amounted 2.21 ± 0.43 MCC against 1.40 ± 0.07 MCC in the peripheral blood neutrophils, the level of CP also increased and amounted 1.51 ± 0.39 MCC against 0.83 ± 0.43 MCC. TANs activity in NBT-test was not significantly different from that of the peripheral blood neutrophils.

TANs compose the minor part of primary ovarian tumor infiltrate. Indicators of aerobic and anaerobic bactericidal activity of TANs significantly exceed that of the peripheral blood neutrophils in patients with ovarian cancer.

This work was conducted in the framework of implementing the state assignment of the Ministry of Education and Science of the Russian Federation No. 1163 – Russia.

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来源期刊
Ejc Supplements
Ejc Supplements 医学-肿瘤学
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审稿时长
3.7 months
期刊介绍: EJC Supplements is an open access companion journal to the European Journal of Cancer. As an open access journal, all published articles are subject to an Article Publication Fee. Immediately upon publication, all articles in EJC Supplements are made openly available through the journal''s websites. EJC Supplements will consider for publication the proceedings of scientific symposia, commissioned thematic issues, and collections of invited articles on preclinical and basic cancer research, translational oncology, clinical oncology and cancer epidemiology and prevention. Authors considering the publication of a supplement in EJC Supplements are requested to contact the Editorial Office of the EJC to discuss their proposal with the Editor-in-Chief. EJC Supplements is an official journal of the European Organisation for Research and Treatment of Cancer (EORTC), the European CanCer Organisation (ECCO) and the European Society of Mastology (EUSOMA).
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