肿瘤浸润性树突状细胞在结肠癌组织中的密度及临床意义
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摘要
目的探讨肿瘤浸润性树突状细胞(TIDC)在结肠癌组织中的密度及临床意义。方法选取117例结肠癌患者作为研究对象,取患者术中结肠癌组织及癌旁组织标本,比较两种组织中TIDC密度及主要组织相容性复合体Ⅱ(MHC-Ⅱ)、CD54阳性表达情况,并分析结肠癌组织中TIDC密度、TIDC的MHC-Ⅱ和CD54表型与结肠癌患者临床特征的关系。结果结肠癌组织中TIDC密度及MHC-Ⅱ、CD54阳性表达率均明显低于癌旁组织,差异均有统计学意义(P﹤0.01)。不同年龄、性别、肿瘤直径和肿瘤细胞类型的结肠癌患者肿瘤组织中TIDC密度及MHC-Ⅱ、CD54阳性表达率比较,差异均无统计学意义(P﹥0.05)。中低分化的结肠癌患者肿瘤组织中TIDC密度明显低于高分化的结肠癌患者肿瘤组织,差异有统计学意义(t=7.574,P﹤0.01);TNM分期为Ⅲ期的结肠癌患者肿瘤组织中TIDC密度及MHC-Ⅱ、CD54阳性表达率均明显低于TNM分期为Ⅱ期的结肠癌患者肿瘤组织,差异均有统计学意义(t=8.845、3.278、5.750,P﹤0.01)。结论 TIDC在结肠癌组织中密度下降,不成熟的调节性树突状细胞比例增加,可能与肿瘤细胞生长、转移有关。
Objective To investigate the density of tumor infiltrating dendritic cell(TIDC) in the tissues of patients with colon cancer and its clinical significance. Method A total of 117 patients with colon cancer were included in the study, of which the tumor tissue and adjacent normal tissue specimens were collected. The density of TIDC in these tissues, and the positive expression of major histocompatibility complex II(MHC-II)and CD54 were detected and compared, besides, the association between TIDC density, and phenotype of MHC-II and CD54, as well as the clinical manifestations were analyzed. Result The TIDC density and positive expression rates of MHC-II and CD54 in colon cancer tissues were significantly lower than those of the adjacent normal tissues(P<0.01). There were no significant differences in TIDC density and positive expression rates of MHC-II and CD54 in colon cancer tissues of patients with different age,gender, tumor diameter and cancer cell types(P>0.05). The TIDC density in patients with moderately and poorly differentiated colon cancer were significantly lower than those in patients with highly differentiated lesions(t=7.574, P<0.01).The TIDC density and the positive expression rates of MHC-II and CD54 in patients with TNM stage III were significantly lower than those of patients with TNM stage II colon cancer(t=8.845, 3.278, 5.750, P<0.01). Conclusion The density of TIDC decreases and the proportion of immature regulatory dendritic cells increases in colon cancer tissue, which may be related to the growth and metastasis of cancer cells.
Objective To investigate the density of tumor infiltrating dendritic cell(TIDC) in the tissues of patients with colon cancer and its clinical significance. Method A total of 117 patients with colon cancer were included in the study, of which the tumor tissue and adjacent normal tissue specimens were collected. The density of TIDC in these tissues, and the positive expression of major histocompatibility complex II(MHC-II)and CD54 were detected and compared, besides, the association between TIDC density, and phenotype of MHC-II and CD54, as well as the clinical manifestations were analyzed. Result The TIDC density and positive expression rates of MHC-II and CD54 in colon cancer tissues were significantly lower than those of the adjacent normal tissues(P<0.01). There were no significant differences in TIDC density and positive expression rates of MHC-II and CD54 in colon cancer tissues of patients with different age,gender, tumor diameter and cancer cell types(P>0.05). The TIDC density in patients with moderately and poorly differentiated colon cancer were significantly lower than those in patients with highly differentiated lesions(t=7.574, P<0.01).The TIDC density and the positive expression rates of MHC-II and CD54 in patients with TNM stage III were significantly lower than those of patients with TNM stage II colon cancer(t=8.845, 3.278, 5.750, P<0.01). Conclusion The density of TIDC decreases and the proportion of immature regulatory dendritic cells increases in colon cancer tissue, which may be related to the growth and metastasis of cancer cells.
引文
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[19] Radej S, Roliński J, Rawicz-Pruszyński K, et al. Immunomodelling characteristics of mature dendritic cells stimulated by colon cancer cells lysates[J]. Pol Przegl Chir,2015, 87(2):71-82.
[2] Li Q, Wang Y, Cai G, et al. Solitary lymph node metastasis is a distinct subset of colon cancer associated with good survival:a retrospective study of surveillance, epidemiology,and end-results population-based data[J]. BMC Cancer,2014, 14:368.
[3] Carethers JM, Murali B, Yang B, et al. Influence of race on microsatellite instability and CD8+T cell infiltration in colon cancer[J]. PLoS One, 2014, 9(6):e100461.
[4] Shurin GV, Ma Y, Shurin MR. Immunosuppressive mechanisms of regulatory dendritic cells in cancer[J]. Cancer Microenviron, 2013, 6(2):159-167.
[5] Huang XM, Liu XS, Lin XK, et al. Role of plasmacytoid dendritic cells and inducible costimulator-positive regulatory T cells in the immunosuppression microenvironment of gastric cancer[J]. Cancer Sci, 2014, 105(2):150-158.
[6] Morales Soriano R, Morón Canis JM, Molina Romero X, et al. Influence of simultaneous liver and peritoneal resection on postoperative morbi-mortality and survival in patients with colon cancer treated with surgical cytoreduction and intraperitoneal hyperthermic chemotherapy[J]. Cir Esp,2017, 95(4):214-221.
[7] Tabola R, Mantese G, Cirocchi R, et al. Postoperative mortality and morbidity in older patients undergoing emergency right hemicolectomy for colon cancer[J]. Aging Clin Exp Res, 2017, 29(Suppl 1):121-126.
[8] Ma YF, Ren Y, Wu CJ, et al. Interleukin(IL)-24 transforms the tumor microenvironment and induces anticancer immunity in a murine model of colon cancer[J]. Mol Immunol,2016, 75:11-20.
[9] Zhang W, Chen L, Ma K, et al. Polarization of macrophages in the tumor microenvironment is influenced by EGFR signaling within colon cancer cells[J]. Oncotarget, 2016, 7(46):75366-75378.
[10] Smith LE, Olszewski MA, Georgoudaki AM, et al. Sensitivity of dendritic cells to NK-mediated lysis depends on the inflammatory environment and is modulated by CD54/CD226-driven interactions[J]. J Leukoc Biol, 2016, 100(4):781-789.
[11] Yan J, Liu B, Shi Y, et al. Class II MHC-independent suppressive adhesion of dendritic cells by regulatory T cells in vivo[J]. J Exp Med, 2017, 214(2):319-326.
[12] Spallanzani RG, Torres NI, Avila DE, et al. Regulatory dendritic cells restrain NK cell IFN-gamma production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors[J]. J Immunol, 2015,195(5):2141-2148.
[13]张子杰.结肠癌组织VEGF表达与树突状细胞浸润的临床意义及与血清VEGF浓度及其活化水平的相关性[J].中国免疫学杂志, 2015, 31(9):1257-1261.
[14]尹文功.树突状细胞在结肠癌的表达及其意义[D].延吉:延边大学, 2012.
[15] Chen J, Guo XZ, Li HY, et al. Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro[J].World J Gastroenterol, 2017, 23(5):817-829.
[16] Zhou J, Ma P, Li J, et al. Comparative analysis of cytotoxic T lymphocyte response induced by dendritic cells pulsed with recombinant adeno-associated virus carrying alpha-fetoprotein gene or cancer cell lysate[J]. Mol Med Rep, 2015, 11(4):3174-3180.
[17] Lin CL, Hsiao G, Wang CC, et al. Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells[J]. Pharmacol Res, 2016,110:111-121.
[18] Gueguen C, Bouley J, Moussu H, et al. Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy[J]. J Allergy Clin Immunol, 2016, 137(2):545-558.
[19] Radej S, Roliński J, Rawicz-Pruszyński K, et al. Immunomodelling characteristics of mature dendritic cells stimulated by colon cancer cells lysates[J]. Pol Przegl Chir,2015, 87(2):71-82.