肿瘤浸润性树突状细胞的研究进展

树突状细胞(DCs)是最具潜能的抗原提呈细胞，它能激活初始型T细胞，在启动抗瘤免疫应答中扮演着重要角色。肿瘤浸润性树突状细胞(TIDCs)反映了荷瘤宿主的抗瘤免疫能力，其浸润密度可能与肿瘤预后有关。TIDC是功能低下或无功能的树突状细胞，肿瘤细胞分泌的免疫抑制因子对其表型特征的改变可能是致使其功能低下的原因。以上研究为DC介导的肿瘤免疫治疗提供了理论基础，并指导人们从不同途径利用DC诱导抗瘤免疫反应，从而达到治疗肿瘤的目的。     

人肿瘤浸润性树突状细胞的表型分析及原因探讨

树突状细胞作为抗原提呈细胞在机体的抗肿瘤免疫反应中起重要作用,对肿瘤浸润性树突状细胞的研究有助于揭示肿瘤免疫逃逸机制.本文采用酶消化、细胞分离、流式细胞仪分析等方法研究了14例胃肠道肿瘤患者肿瘤浸润性树突状细胞的表型,并用RT-PCR检测了IL-10,VEGF和TGF-β_13种免疫抑制因子在14例肿瘤细胞中的表达.实验结果表明肿瘤浸润性单核细胞中有CDla~ 的树突状细胞的存在,该类细胞的表面分子如MHCⅡ类分子、CD80及CD54等共刺激分子和粘附分子有低表达或不表达,14例肿瘤细胞中     

胃癌组织中血管内皮生长因子C与肿瘤浸润性树突状细胞的相关性

目的: 探讨胃癌组织中血管内皮细胞生长因子C(vascular endothelial growth factorc, VEGFC)与肿瘤浸润性树突状细胞( tumor infiltrating dendritic cells，TIDC)在胃癌浸润转移中的作用及两者的关系。方法：52例胃癌石蜡标本选自重庆医科大学附属第一医院外科2004年9月至     

树突状细胞在食管癌T细胞抗肿瘤免疫中的作用

目的：了解食管癌组织中树突状细胞（ＤＣｓ）在肿瘤浸润性Ｔ淋巴细胞激活中的作用。方法：采用免疫组化和ＲＴ－ＰＣＲ的方法,对４６例食管癌手术标本中ＤＣｓ（ＣＤ１ａ）、Ｔ细胞亚群（ＣＤ３、ＣＤ４、ＣＤ８、ＣＤ２５）及共刺激因子Ｂ７进行检测。结果：癌组织中的ＤＣｓ与ＣＤ３＾＋、ＣＤ４＾＋Ｔ细胞有相关性,与ＣＤ８＾＋、ＣＤ２５＾＋Ｔ细胞无明显关系,且Ｂ７ｍＲＮＡ表达均为阴性。结论：食管癌中ＤＣｓ不一定能有效     

树突状细胞对肿瘤浸润性淋巴细胞抗结肠癌活性影响的研究

目的:探讨树突状细胞(DC)激活的肿瘤浸润性淋巴细胞(TIL)体外对结肠癌细胞的杀伤活性。方法:从结肠癌患者外周血获取DC,应用粒/巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)和肿瘤抗原激活DC,然后用DC激活TIL,观察TIL在体外对自体结肠癌细胞和VoLo细胞的杀伤活性。结果:DC激活的TIL对自体结肠癌细胞具有很强的杀伤活性,杀伤率为87.62%±3.01%,明显高于未经DC激活的TIL、DC激活的T淋巴细胞和未经DC激活的T淋巴细胞对自体结肠癌细胞的杀伤率分别为53.72%±1.50%、52.23%±1.46%和3.55%±0.25%,而它们对VoLo细胞的杀伤活性则相对较低。结论:结肠癌患者外周血DC能诱导TIL产生高效而特异的抗结肠癌免疫活性。     

树突状细胞在食管癌T细胞抗肿瘤免疫中的作用

目的：研究食管癌组织中树突状细胞（ＤＣｓ）在肿瘤浸润性Ｔ淋巴细胞激活中的作用,方法：用免疫组化和ＲＴ－ＰＣＲ的方法,检测４６例食管癌手术标本中ＤＣｓ（ＣＤ１ａ）、Ｔ细胞亚群（ＣＤ３、ＣＤ４、Ｃ人刺激因子Ｂ７。结果：癌组织中的ＤＣｓ与ＣＤ３（＋）、ＣＤ４（＋）Ｔ细胞有相关性,与ＣＤ８（＋）、ＣＤ２５（＋）Ｔ细胞无明显关系,且Ｂ７ｍＲＮＡ表达均为阴性,结论：食管癌中ＤＣｓ不一定能有效地激活Ｔ细胞,其中Ｂ７基因表达受抑制,可能是不能有效激活Ｔ淋巴细胞产生免疫耐受的重要原因之一。     

不同亚型树突状细胞之间的作用在肿瘤免疫中的研究进展

树突状细胞（dendritic cells,DCs）作为专职抗原呈递细胞,被认为是连接天然免疫与获得免疫的桥梁,在诱发获得性免疫和免疫耐受调节中发挥着重要作用。经典Ⅰ型DCs（conventional DC1, cDC1）被认为在抗肿瘤免疫应答以及交叉呈递中发挥尤为关键的作用。然而,DCs各亚群的功能特异性以及亚群之间的相互作用在进一步强化抗肿瘤免疫应答中的作用不可忽视。本文就DCs亚群之间的作用在肿瘤免疫中的研究进展进行综述,以期为以DCs为靶点的肿瘤免疫治疗提供新的思路。      

H22细胞全细胞抗原负载的树突状细胞激活肿瘤浸润性淋巴细胞抗小鼠肝癌的实验

目的探讨H22小鼠肝癌细胞（H22细胞）全细胞抗原致敏的树突状细胞激活肿瘤浸润淋巴细胞抗小鼠肝癌细胞活性。方法取得小鼠骨髓细胞并诱导生成树突状细胞,由冻融法制备的H22细胞全细胞抗原致敏,然后用已致敏的树突状细胞激活肿瘤浸润性淋巴细胞,测定致敏前后的DC表面抗原CD11c、CD80、CD86、CD40、MHCⅡ,并评估激活前后的TIL对H22细胞的杀伤活性,同时脾淋巴细胞作为杀伤对照。结果CD11c阳性细胞中CD80、CD86、CD40、MHCⅡ阳性细胞所占比例在致敏后的DC表现为明显上调。经致敏后成熟DC激活的TIL对H22细胞杀伤活性明显高于未激活的TIL,并高于激活或未激活的小鼠脾脏淋巴细胞。结论在H22细胞全抗原致敏后,小鼠成熟DC中CD80、CD86、CD40、MHCⅡ的表达率明显高于未成熟DC。经H22细胞全细胞抗原致敏的DC能诱导活化TIL,明显提高其在体外对H22细胞的杀伤活性。     

The expression and clinical value of tumor infiltrating dendritic cells in tumor tissues of patients with esophageal cancer

BackgroundAs dendritic cells (DCs) are the major antigen-presenting cells of the immune system, understanding their role in esophageal cancer is essential for the development of preventative and treatment strategies. This study investigated the expression level and clinical value of tumor infiltrating dendritic cells (TIDCs) in tumor tissues of patients with esophageal cancer.MethodsFrom January 2019 to January 2021, 184 patients with esophageal cancer treated were prospectively enrolled as the observation group and 184 patients with benign esophageal tumors were selected as the control group. Tumor tissue samples were obtained and the expression level and phenotypes of the TIDCs were analyzed. The correlation between TIDC expression and clinical characteristics of patients with esophageal cancer was investigated.ResultsThe density of the TIDCs in the observation group was lower than that in the control group (8.76±2.25 vs. 9.97±2.19; P=0.000). Furthermore, the percentage of major histocompatibility complex-II (MHC-II) positive DCs and the percentage of CD54 positive DCs were relatively lower in the observation group compared to the control group (6.60%±2.12% vs. 9.34%±2.41%; P=0.000 and 7.41%±2.36% vs. 9.98%±2.47%; P=0.000, respectively). Esophageal cancer patients with lymph node metastasis had lower TIDC density, lower percentage of MHC-II positive DCs, and lower percentage of CD54 positive DCs compared to patients without node metastasis (P<0.05). Patients with stage III esophageal cancer also showed significantly lower TIDC density, lower percentage of MHC-II positive DCs, and lower percentage of CD54 positive DCs compared to patients with stage I/II esophageal cancer (P<0.05). Esophageal cancer patients with tumor diameter ≥4 cm presented with decreased TIDC density, decreased percentage of MHC-II positive DCs, and decreased percentage of CD54 positive DCs compared to patients with tumor diameter <4 cm (P<0.05). In addition, the density of TIDCs, the percentage of MHC-II positive DCs, and the percentage of CD54 positive DCs were significantly negatively correlated with the percentage of CD4⁺ T-lymphocytes and positively correlated with the percentage of CD8⁺ T-lymphocytes (P<0.05).ConclusionsPatients with esophageal cancer had low expression and function of TIDCs, and this was related to the imbalance of T-lymphocyte subsets, lymph node metastasis, TNM stage, and lesion size.     

食管鳞癌和转移淋巴结组织中CD1a和CD83的表达及其临床意义

目的：探讨食管鳞癌（esophageal squamous cell carcinoma,ESCC）和转移淋巴结组织中CD1a和CD83的表达及其与ESCC临床病理特征间的关系。方法：选取河北医科大学第四医院胸外科2002年5月至2003年12月间手术切除并经病理确诊的78例ESCC石蜡标本,采用流式细胞术检测78例ESCC、24例正常食管黏膜、35例正常淋巴结和32例转移淋巴结组织中CD1a和CD83的表达。结果：（1）ESCC组织中CD1a和CD83的表达量明显低于正常黏膜CD1a和CD83的表达量(均P<0.05)。（2）CD1a表达量与癌组织浸润深度、临床分期、分化程度及淋巴结转移无相关性(均P>0.05);CD83表达量与ESCC临床分期及淋巴结转移有关(P<0.05)。（3）转移淋巴结组织中CD1a表达量与正常淋巴结无显著性差异(P>0.05);转移淋巴结组织中CD83表达量显著低于正常淋巴结组织(P<0.05)。结论：ESCC组织中CD83的表达量反映ESCC局部免疫状态,在ESCC的发生、发展过程中具有重要作用,可作为评价食管癌生物学行为的指标。     

Expression and significance of tumor infiltrating dendritic cells in renal cell carcinoma

Dendritic cells(DCs) are considered to be the most effective antigen-presenting cells(APCs) that play a major role in initiating the antitumor immune response. Tumor infiltrating dendritic cells(TIDCs) are DCs that exist in microenviroment of tumors. Although the function and significance of TIDCs in the immune response to tumor have never been clearly demonstrated, their location suggests that they play a critical role in the presentation of tumor antigen to specific T cells[1]. For the…     

树突状细胞对肿瘤浸润性淋巴细胞杀伤自体肝癌细胞活性影响的研究

目的　探讨树突状细胞 (DC)激活的肿瘤浸润性淋巴细胞 (TIL )体外对自体肝癌细胞杀伤活性。方法　从肝癌患者外周血获取 DC,应用粒 /巨噬细胞集落刺激因子 (GM- CSF)、白细胞介素 - 4 (IL - 4 )和肿瘤抗原激活 DC,然后用 DC激活 TIL ,观察 TIL在体外对自体肝癌细胞的杀伤活性。结果　 DC激活的 TIL对自体肝癌细胞具有很高的杀伤活性 ,杀伤率为 (89.39± 3.0 5 ) % ,明显高于未经 DC激活的 TIL、DC激活的 T淋巴细胞和未经 DC激活的 T淋巴细胞对自体肝癌细胞的杀伤率。其杀伤率分别为 (5 5 .2 3± 1.5 3) %、(5 4 .89± 1.4 8) %和 (3.6 5± 0 .2 6 ) %。结论　肝癌患者外周血 DC能诱导 TIL产生高效而特异的抗肝癌免疫     

树突状细胞与食管癌研究进展

食管癌是消化道常见的恶性肿瘤,治疗效果不理想,预后差。树突状细胞（DC）是专职的抗原提呈细胞,其在抗肿瘤免疫中发挥十分重要的作用。大量研究表明,食管癌的进展及预后与树突状细胞在癌组织和周围淋巴结内的分布、密度和功能障碍密切相关。因此,探索以DC疫苗为基础的食管癌免疫治疗具有十分重要的意义。本文综述食管癌与树突状细胞相关研究进展。     

封闭B7-H1分子对肿瘤浸润树突状细胞介导T细胞免疫功能的影响

目的:研究肿瘤浸润树突状细胞（tumorinfiltrating dendritic cell,TIDC）及脾脏树突状细胞（splenic dendritic cell,SDC）表面B7H1、B71、B72分子的表达情况;探讨封闭TIDC及SDC表面B7H1分子对其介导T细胞免疫功能的影响。方法： CD11c磁珠阳性分选法提取荷瘤小鼠的TIDC及SDC,流式细胞术检测其表面B7H1、B71、B72分子的表达情况。TIDC及SDC作为刺激细胞,脾脏T细胞作为反应细胞行混合淋巴细胞反应,同时加入B7H1抗体或其对照抗体,XTT比色法检测T细胞增殖指数,ELISA法检测T细胞分泌IL10的量。〖HT5W〗结果：〖HT5"SS〗B71及B72分子在TIDC表面的表达水平显著低于SDC（P<001）;B7H1分子在TIDC及SDC表面皆中度表达,表达水平无明显差异（P>0.05）。TIDC刺激T细胞增殖能力显著低于SDC,且诱导T细胞分泌更多的IL10。封闭DC表面B7H1分子后,TIDC刺激T细胞增殖能力显著提高（P<0.01）,且诱导T细胞分泌IL10的量明显减少（P<0.01）;SDC刺激T细胞增殖能力及诱导T细胞分泌IL10的量无明显变化（P>0.05）。结论：封闭DC表面的B7H1分子能显著提高TIDC活化T细胞的能力,可能解除TIDC介导的肿瘤免疫抑制     

恶性肿瘤特异生长因子和肿瘤浸润性树突状细胞在子宫内膜癌患者中的表达及临床意义

目的:探讨恶性肿瘤特异生长因子(TSFG)和肿瘤浸润性树突状细胞(TIDC)在子宫内膜癌患者中的表达及临床意义。方法:选择2015年1月至2017年1月我院收治的子宫内膜癌患者50例。检测子宫内膜组织中TIDC和血清中TSFG水平,分析TSFG、TIDC在不同临床病理特征患者中的表达。结果:与癌旁组织比较,肿瘤组织中TIDC明显降低(P=0.000);MHC-Ⅱ阳性树突状细胞（DC）(%)明显降低（P=0.000);CD54阳性DC(%)明显降低（P=0.000)。与非淋巴结转移的患者相比,淋巴结转移的患者TIDC、MHC-Ⅱ阳性DC(%)、CD54阳性DC(%)均明显降低,TSFG明显增高(P<0.05)。与临床TNM分期为Ⅰ或Ⅱ期的患者相比,Ⅲ或Ⅳ期的患者TIDC、MHC-Ⅱ阳性DC(%)和CD54阳性DC(%)均明显降低,TSFG明显增高(P<0.05)。与肌层浸润≤1/2的患者相比,肌层浸润>1/2的患者TIDC、MHC-Ⅱ阳性DC(%)和CD54阳性DC(%)均明显降低,TSFG明显增高(P<0.05)。与中、高分化的患者相比,低分化患者组织中TIDC、MHC-Ⅱ阳性DC(%)和CD54阳性DC(%)均明显降低,TSFG明显增高（P<0.05）。结论:TIDC在肿瘤组织中低表达,且多为不成熟的调节性DC细胞。低分化、TNM分期为Ⅲ或Ⅳ期、淋巴结发生转移、肌层浸润>1/2的患者血清中TSFG水平明显升高,而肿瘤组织中TIDC明显降低。提示子宫内膜癌患者血清中TSFG和肿瘤组织中TIDC可作为判断预后的指标。     

Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer

Activated T regulatory (T_reg) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated T_reg cells and the progression of human colon cancer. We designed a cross‐sectional study of CD4⁺Foxp3⁺ T cells from peripheral blood, primary tumor and nontumor colon tissue of 42 patients with colon cancer and correlated the percentages of different subgroups of T_reg cells with colon cancer stage. The phenotypes, cytokine‐release patterns and suppression ability of these T_reg cells were analyzed. We found that T_reg cells increased significantly in both peripheral blood and cancer tissue. In addition, the T_reg cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing T_reg cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated T_reg cells (Foxp3^hiCD45RA^?) and nonsuppressive T_reg cells (Foxp3^loCD45RA^?), but not resting T_reg cells (Foxp3^lowCD45RA⁺), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated T_reg cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T‐cell antigen‐4. Activated T_reg cells, however, secreted significantly lower levels of effector cytokines (interleukin‐2, tumor necrosis factor‐α and interferon‐γ) than did resting T_reg cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, T_reg cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated T_reg cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.