吲哚胺2，3-二氧化酶基因修饰的DCs对小鼠移植物抗宿主病的抑制作用

目的:探讨小鼠树突状细胞(dendritic cells,DCs)转染吲哚胺2,3-二氧化酶(indolamine 2,3-dioxygenase,IDO)基因后对移植物抗宿主病(graft versus host disease,GVHD)的抑制作用。方法:用携带IDO基因的重组腺病毒感染BALB/c小鼠来源的树突状细胞,后者与C57BL/6小鼠骨髓移植物共培养,将经过处理的骨髓移植给BALB/c小鼠(C57BL/6→BALB/c小鼠GVHD模型,H-2~h→H-2~d),观察、比较各组GVHD表现(包括GVHD评分、生存期、病理学改变),并行嵌合体检测及观察混合淋巴细胞反应(mixed lymphocyte reaction,MLR)。结果:致死剂量照射的受体小鼠接受经IDO处理的骨髓移植(bone marrow transplantation,BMT)后,未出现明显的GVHD反应,生存期显著延长,3个月时生存率大于80%;对照组均在移植后2周左右出现明显的GVHD表现,生存期未超过1个月。IDO-DC治疗组未出现明显的组织病理学损害;3个月时IDO-DC治疗组仍然保持比较高的嵌合;IDO-DC组的T细胞对C57BL/6、BALB/c淋巴细胞的反应性与对C3H淋巴细胞反应性相比显著降低(P<0.05)。结论:经IDO基因修饰的DCs可以选择性去除骨髓移植物中异基因反应性T细胞,从而特异性地抑制GVHD并能及早地免疫重建。     

吲哚胺2，3-双加氧酶与肿瘤免疫耐受

人体免疫系统可以对肿瘤表达的多种异常抗原产生免疫反应,但肿瘤通过复杂的进化过程所致的免疫耐受现象能够降低宿主针对肿瘤的自身免疫反应,使宿主无法通过免疫系统对肿瘤细胞作出免疫应答。因此该现象可导致肿瘤细胞逃避宿主的免疫监视以及免疫系统的攻击,从而使肿瘤细胞得以在人体内增殖和转移。IDO是细胞内催化L-色氨酸经犬尿氨酸途径进行分解代谢的关键酶,也是一种与免疫抑制相关的酶。IDO在多种病理生理过程中促进机体免疫耐受的发生,因此与肿瘤的发生发展有密切关系。大量研究发现,IDO作为一种重要的抑制性免疫检查点,在肿瘤患者中其酶活性的增加会促进肿瘤免疫耐受现象的建立。随着IDO介导肿瘤免疫耐受相关分子机制的发现与证实,IDO抑制剂也已成为肿瘤免疫疗法中的关键研究领域。本文重点阐明IDO发现的起源过程、在正常人体和肿瘤患者中的表达情况、调节色氨酸代谢等免疫调节功能以及IDO诱导TME中肿瘤免疫耐受建立的几种重要机制,包括色氨酸耗竭、激活芳香烃受体、诱导调节性T细胞扩增与活化以及募集和激活大量骨髓来源的抑制性细胞等机制,以便能够为今后的深入研究和IDO抑制剂的治疗应用提供更广阔的思维。     

吲哚胺2,3双加氧酶与肿瘤免疫耐受

肿瘤可诱导机体免疫系统对其产生免疫耐受，而免疫调节酶吲哚胺2，3双加氧酶（Indoleamine 2，3dioxygenase ，IDO）可能参与了这种免疫耐受。IDO是色氨酸代谢的限速酶,IFN能影响IDO的表达。IDO可能通过初始免疫应答和效应阶段两个环节来调节肿瘤免疫耐受。在初始免疫应答反应阶段，可能活化的调节性T细胞表达的CTLAA诱导了IDO的表达，肿瘤可能通过IDO来破坏机体的免疫系统从而对其产生免疫耐受。在效应阶段，肿瘤细胞自身表达的IDO可对肿瘤产生局部免疫耐受，其机制可能主要是通过降解局部组织微环境中的色氨酸来抑制效应T细胞的增殖,这两个环节对肿瘤免疫耐受的调节是相辅相成的。IDO抑制剂1MT可使T细胞增殖抑制得到恢复,有望成为一种有效的抗肿瘤药物。     

吲哚胺2,3-双加氧酶在肝癌组织的表达及其临床意义

目的：探讨吲哚胺2，3-双加氧酶（indoleamine 2，3-dioxygenase，IDO）在原发性肝癌细胞、癌旁肝细胞及肿瘤浸润淋巴细胞中的表达及其临床意义。方法：选择经临床确诊的21例原发性肝癌患者的手术切除和（或）肝穿刺所取肝癌组织及癌旁组织标本，通过免疫组织化学染色法检测肝癌及癌旁组织IDO的表达，并分析其与临床病理特征的关系。结果：IDO在原发性肝癌细胞与肿瘤浸润淋巴细胞的表达水平相对较低，在癌旁肝硬变细胞中表达明显增高（P〈0．01）。IDO表达强度与患者的年龄、性别、TNM分期无关（P〉0．05）；与患者大体病理分型有一定的相关性，浸润型IDO表达强度较块状型明显增高（P〈0．05）；有血管浸润及癌栓形成患者IDO也呈高表达状态（P〈0．05）；IDO的表达还与病理组织学分化情况相关，低分化肿瘤组织IDO的表达强度明显增高（P〈0．05）。结论：IDO的表达与肝细胞癌恶性有一定的相关，故IDO拟可以作肝癌预后差的一个参考指标。     

吲哚胺2,3双加氧酶在急性白血病细胞的表达及其临床意义

目的 探讨急性白血病细胞吲哚胺2,3双加氧酶(IDO)的表达与急性白血病临床病理参数和预后的关系.方法 分别采用免疫组织化学法及实时荧光定量反转录PCR法检测60例急性白血病患者白血病细胞IDO蛋白和RNA表达水平,并与临床资料相结合进行分析.结果 急性白血病患者IDO蛋白阳性表达率为63.3％(38/60),其中急性髓系白血病(AML)患者的阳性率为69.4％(34/49),尤其是AML-M5型患者阳性率达82.9％(29/35);而急性淋巴细胞白血病患者为36.4％(4/11).IDO蛋白在健康人外周血单个核细胞呈阴性表达.IDO RNA在AML-M5组的表达水平高于非AML-M5组(P＜0.05)和健康人组(P＜ 0.001),非AML-M5组亦高于健康人(P＜ 0.001).IDO RNA的表达水平与患者的性别、年龄、药物敏感性不相关,与患者是否合并肺部感染相关.IDO阳性表达者有较差的预后,但IDO并不是AML-M5患者独立的预后不良指标.结论 IDO在AML-M5患者的表达较非AML-M5患者和健康人明显升高.IDO的阳性表达影响AML-M5患者的预后,但不是独立预后不良指标.     

吲哚胺2，3 双加氧酶在肝癌组织的表达及其临床意义

目的: 探讨吲哚胺2,3双加氧酶(indoleamine 2,3dioxygenase，IDO)在原发性肝癌细胞、癌旁肝细胞及肿瘤浸润淋巴细胞中的表达及其临床意义。方法：选择经临床确诊的21例原发性肝癌患者的手术切除和（或）肝穿刺所取肝癌组织及癌旁组织标本，通过免疫组织化学染色法检测肝癌及癌旁组织IDO的表达, 并分析其与临床病理特征的关系。结果：IDO在原发性肝癌细胞与肿瘤浸润淋巴细胞的表达水平相对较低，在癌旁肝硬变细胞中表达明显增高（P<0.01）。IDO表达强度与患者的年龄、性别、TNM分期无关（P＞0.05）；与患者大体病理分型有一定的相关性，浸润型IDO表达强度较块状型明显增高（P<0.05）；有血管浸润及癌栓形成患者IDO也呈高表达状态（P<0.05）；IDO的表达还与病理组织学分化情况相关，低分化肿瘤组织IDO的表达强度明显增高（P<0.05）。结论：IDO的表达与肝细胞癌恶性有一定的相关，故IDO拟可以作肝癌预后差的一个参考指标。     

吲哚胺2,3-双加氧酶在结肠癌及其区域淋巴结中的表达与临床意义

目的：探讨吲哚胺2，3-双加氧酶（IDO）在结肠癌及其区域淋巴结中的表达及其临床意义.方法：通过免疫组织化学染色法检测IDO在110例结肠癌原发灶、癌旁正常结肠上皮组织和区域淋巴结的表达，分析IDO表达与患者临床病理特征的关系.结果：IDO在结肠癌原发灶的表达水平与癌旁正常结肠上皮组织相似，其表达强度与患者的年龄、性别、TNM分期和5年生存率无关.在无转移的区域淋巴结中，IDO主要表达于树突样细胞，区域淋巴结强表达IDO患者的5年生存率较低（31.8%）.结论：在结肠癌细胞转移到区域淋巴结前，区域淋巴结中IDO的表达已使其处于免疫抑制状态，从而为肿瘤转移创造了有利条件，而肿瘤细胞是否表达IDO并不影响肿瘤的转移能力.     

吲哚胺2,3-双加氧酶上调人肝癌细胞人类白细胞抗原-G的表达

目的:探讨人类吲哚胺2,3-双加氧酶（indoleamine 2,3-dioxygenase,IDO）对肝癌细胞人类白细胞抗原-G（humanleucocyte antigen-G,HLA-G）表达的影响。方法:用脂质体lipofectamine^TM2000将pcDNA3.1-IDO重组质粒稳定转染入肝癌SMMC-7721细胞作为实验组（pcDNA3.1-IDO质粒转染组）,同时设置空载体对照组（pcDNA3.1转染组）和空白对照组（未转染组）,用RT-PCR和Western blot鉴定实验组和2个对照组细胞IDO mRNA和蛋白的表达,然后分别给予实验组细胞IDO的抑制剂(2.5 mmol/L 1-D-MD和底物（200μmol/L L-色氨酸）干预48 h,进一步用实时荧光定量PCR和Westernblot检测上述5组细胞中HLA-G mRNA和蛋白的表达水平。结果:RT-PCR和Western blot显示空载体对照组和空白对照组未见IDO表达,而实验组细胞高表达IDO。实时荧光定量PCR和Western blot结果显示,实验组HLA-G mRNA和蛋白表达水平较空载体对照组和空白对照组均明显上调（P均<0.05）,给予1-D-MT和L-色氨酸干预后此效应可逆转。结论:在肝癌SMMC-7721细胞,IDO可以上调HLA-G的表达,色氨酸降解途径参与了此调节过程。     

吲哚胺-2,3-双加氧酶与肿瘤免疫逃逸关系的研究进展△

吲哚胺-2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)是色氨酸代谢的关键酶.它在多种肿瘤中表达,越来越多的证据表明IDO具有免疫抑制作用.IDO通过抑制CD8+T细胞增殖并促进其凋亡,促使自然杀伤细胞功能障碍,同时调控调节性T细胞的招募和巨噬细胞极化等发挥免疫抑制作用,从而促进了肿瘤的免疫逃逸.     

吲哚胺2,3-双加氧酶、c-myc在膀胱尿路上皮癌中的表达及其意义

目的 探讨吲哚胺2,3-双加氧酶（IDO）、c-myc在膀胱尿路上皮癌中的表达及其临床意义.方法 采用荧光定量聚合酶链反应（PCR）检测新鲜肿瘤及黏膜标本各20例IDO mRNA表达,采用SP法检测肿瘤石蜡标本84例及黏膜22例IDO、c-myc蛋白的表达,分析二者与临床病理特征的关系.结果 在膀胱尿路上皮癌组织中,IDO、c-myc蛋白表达强度与患者年龄、性别无关.在浸润型膀胱尿路上皮癌组织中IDO蛋白表达高于非浸润型（x2=5.600,P=0.018）,随着组织分级及国际抗癌联盟（UICC）分期增高,IDO蛋白阳性表达率增高（x2=20.268,P=0.000;x2=12.075,P=0.007）.c-myc蛋白在正常膀胱组织中无阳性表达,在膀胱尿路上皮癌组织中44例（52.4％）表达阳性,二者阳性表达率差异有统计学意义（x2=10.733,P=0.001）;c-myc蛋白表达强度与组织学分类、组织分级及UICC分期无关.在膀胱尿路上皮癌组织中IDO蛋白表达强度与c-myc蛋白表达强度呈正相关（r=0.205,P=0.047）,与组织学分类、组织分级及UICC分期呈正相关（r=0.258,P=0.018;r=0.491,P=0.000;r=0.365,P=0.001）.IDO mRNA在膀胱尿路上皮癌组织中的表达（7.696 1±1.745 2）明显高于正常膀胱组织（6.397 0±1.205 1）（t=2.367,P=0.023）.Ta～T1期膀胱尿路上皮癌组织中IDO mRNA的平均表达水平为6.803 4±1.567 5,明显低于T2～T4期的9.183 8±0.690 3（t=4.955,P=0.000）;IDO mRNA在Ⅰ、Ⅱ、Ⅲ级膀胱尿路上皮癌组织中的平均表达水平分别为7.058 7±1.771 5、7.934 2±1.530 5、9.290 7±0.574 5,随着分级增高而增高,差异有统计学意义（t=2.729,P=0.011）.结论 IDO表达与膀胱尿路上皮癌预后不良相关,c-myc表达强度与膀胱尿路上皮癌病变进展无关,但可能与膀胱尿路上皮癌病变发生有关.IDO可能成为膀胱尿路上皮癌预后的预测因子,IDO、c-myc有可能成为肿瘤化疗的一个分子靶向目标.     

抑制吲哚胺2，3-双加氧酶活性促进慢性粒细胞白血病源树突状细胞的功能

目的: 研究吲哚胺2,3双加氧酶（indoleamine 2,3dioxygenase,IDO）在慢性粒细胞性白血病源性树突状细胞（dendritic cells derived from chronic myeloid leukemia,CMLDCs）中的表达,及抑制IDO活性对CMLDCs免疫刺激功能的影响。方法: RTPCR检测17例患者CMLDCs的IDO mRNA的表达情况,流式细胞仪检测CMLDCs免疫表型。在有或无IDO抑制剂1甲基色氨酸（1methyltroptophan,1MT）作用下,分别以不成熟CMLDCs（imDCs）和成熟CMLDCs（mDCs）为刺激细胞,完全缓解期（complete remission,CR）CML患者外周T淋巴细胞为反应细胞建立混合淋巴细胞反应体系,ELISA法检测CMLDCs上清液IL12水平,MTT法检测CMLDCs刺激自体T淋巴细胞的增殖能力。结果: 随着CMLDCs的诱导分化和成熟,IDO mRNA表达逐渐上调;经TNFα诱导的DCs免疫表型除CD1a外,CD80、CD86、CD83、HLADR的表达均明显上调(P<005),且上述分子的表达不受1MT的影响。用1MT抑制IDO活性后的imDCs和mDCs,其IL12水平均明显增加(P<005,P<001),且激发自体T淋巴细胞增殖的能力也明显增强(P<0.05,P<0.01)。结论: 抑制IDO活性可提高CMLDCs的IL12分泌水平,增强其对自体T细胞增殖的刺激能力,IDO对DCs的负性调节为白血病生物治疗提供了新的思路。     

粒细胞集落刺激因子对供体造血干细胞移植物中树突状细胞的影响

 目的　探讨粒细胞集落刺激因子（G-CSF）对正常异基因造血干细胞移植供者外周血与骨髓移植物中I型树突状细胞（DC1）、Ⅱ型树突状细胞（DC2）的数量及DC2／DC1比例的影响。方法　以G-CSF 每天10 μg／kg动员5 d后,以流式细胞术（FCM）检测11例G-CSF动员的异基因外周血造血干细胞移植物及20例G-CSF动员的异基因骨髓移植物中的DC1、DC2数量及DC2／DC1比例,并与8例正常供者动员前外周血及10例健康者动员前骨髓进行比较。结果　动员前后骨髓DC2由14.37×106／L增至29.68×106／L（t＝2.433,P＝0.022）,而骨髓DC1分别为13.77×106／L和18.88×106／L（t＝0.625,P＝0.541）;DC2／DC1比例在动员后为1.83±0.81,较动员前的1.12±0.32明显升高（t＝2.685,P＝0.013）。正常供者以G-CSF动员前、后移植物中外周血 DC2数量分别为14.92×106／L和26.76×106／L（t＝2.390,P＝0.029）,DC2／DC1比例分别为1.00±0.37和2.02±1.43（t＝2.158,P＝0.044）,但外周血DC1分别为14.21×106／L和18.02×106／L（t＝0.625,P＝0.541）。结论　移植前以 G-CSF动员正常异基因干细胞移植供者,可选择性提高外周血及骨髓移植物中DC2的数量,而DC1数量无明显增加。     

Inhibition of indoleamine 2,3‐dioxygenase 1 expression alters immune response in colon tumor microenvironment in mice

Indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades the essential amino acid l-tryptophan along the kynurenine pathway, exerts immunomodulatory effects in a number of diseases. IDO expression is increased in tumor tissue and in draining lymph nodes; this increase is thought to play a role in tumor evasion by suppressing the immune response. A competitive inhibitor of IDO is currently being tested in clinical trials for the treatment of relapsed or refractory solid tumors, but the efficacy of IDO inhibition in colorectal tumors remains to be fully elucidated. In this study, we investigated the effect of IDO deficiency on colon tumorigenesis in mice by genetic deletion and pharmacological inhibition. Ido1-deficient^(−/−) mice were crossed with Apc^Min/+ mice or were administered azoxymethane with or without dextran sodium sulfate. Ido1 deficiency did not lead to significant differences in the size and number of colon tumors. Similarly, the pharmacological inhibition of IDO using 1-methyltryptophan (1-mT) also resulted in no significant differences in tumor size and number in Apc^Min/+ mice. However, Ido1 deficiency altered the immune response in the tumor microenvironment, showing a significant increase in mRNA expression of pro-inflammatory cytokines and a significant decrease in the number of Foxp3-positive regulatory T cells in the colon tumors of Ido1^(−/−) mice. Importantly, 1-mT treatment also significantly altered cytokine expression in the colon tumor tissues. These results suggest that IDO inhibition alone cannot sufficiently suppress colon cancer development in mice despite its immunomodulatory activity in the tumor microenvironment.     

FasL基因修饰树突状细胞的抗白血病作用及其机制

目的:选择性去除骨髓移植物中异基因反应性淋巴细胞,特异性抑制移植物抗宿主病(graft versus host disease,GVHD)并保留移植物的抗白血病(graft versus leukemia,GVL)作用。方法:分别把未经处理的、溶T淋巴细胞处理的和以FasL基因修饰树突状细胞(FasL-DC)处理的3组小鼠骨髓细胞移植物移植给已经接种P815肿瘤细胞的BALB/c受体小鼠,然后观察比较各组小鼠存活情况,并用51Cr释放法检测移植后2个月受体小鼠T淋巴细胞的CTL活性。结果:致死剂量(9Gy)照射的白血病受体鼠在接受经FasL-DC处理的供体骨髓细胞移植后,生存期显著延长,2个月时生存率为40%,对照组在1个月内全部死亡。51Cr释放法检测证实,FasL-DC处理组的T淋巴细胞对P815细胞保持较强的杀伤活性。结论:转染FasL基因的DC可有效去除骨髓移植物中异基因反应性T淋巴细胞,移植用该方法处理过的骨髓,不但能够有效抑制GVHD的发生,同时也可以保留移植物的抗肿瘤作用。     

Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. The present study aimed to investigate IDO expression and its prognostic significance in endometrial cancer. Indoleamine 2,3-dioxygenase expression in endometrial cancer tissues (n = 80) was immunohistochemically scored as four groups (IDO-, 1+, 2+, and 3+). The high IDO expression (IDO2+ or 3+) in tumour cells was found in 37 (46.3%) of the 80 cases, and was positively correlated with surgical stage, myometrial invasion, lymph-vascular space involvement, and lymph node metastasis, but not with the histological grade. Patients with high IDO expression had significantly impaired overall survival and progression-free survival (PFS) (P = 0.002 and P = 0.001, respectively) compared to patients with no or weak expression of IDO (IDO- or 1+). The 5-year PFS for IDO-/1+, 2+, and 3+ were 97.7, 72.9, and 36.4%, respectively. Even in patients with early-stage disease (International Federation of Gynecology and Obstetrics I/II, n = 64), the PFS for IDO2+/3+ was significantly poor (P = 0.001) compared to that for IDO-/1+. On multivariate analysis, IDO expression was an independent prognostic factor for PFS (P = 0.020). These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.     

Inflammation‐induced activation of the indoleamine 2,3‐dioxygenase pathway: Relevance to cancer‐related fatigue

Cancer‐related fatigue (CRF) is a common complication of cancer and its treatment that can significantly impair quality of life. Although the specific mechanisms remain poorly understood, inflammation is now considered to be a distinct component of CRF in addition to effects of depression, anxiety, insomnia, and other factors. One key biological pathway that may link inflammation and CRF is indoleamine 2,3‐dioxygenase (IDO). Induced by inflammatory stimuli, IDO catabolizes tryptophan to kynurenine (KYN), which is subsequently converted into neuroactive metabolites. Here we summarize current knowledge concerning the relevance of the IDO pathway to CRF, including activation of the IDO pathway in cancer patients and, as a consequence, accumulation of neurotoxic KYN metabolites and depletion of serotonin in the brain. Because IDO inhibitors are already being evaluated as therapeutic agents in cancer, the elucidation of the relationship between IDO activation and CRF in cancer patients may lead to novel diagnostic and clinical approaches to managing CRF and its debilitating consequences. Cancer 2015;121:2129–2136. © 2015 American Cancer Society.     

MHC半相合脾加骨髓细胞诱发H22荷瘤鼠的抗肿瘤效应

目的：观察MHC半相合脾加骨髓细胞移植抗小鼠H22实体瘤的效果。方法：以皮下接种H22肝癌细胞的BALB/c×C57BL/6杂交F1代雌性小鼠为受鼠,以健康雌性F1、雄性C57BL/6、雄性C3H小鼠为MHC全相合、半相合、不相合供鼠,观察移植后的抑瘤情况；观察供鼠细胞经~(60)Co照射的MHC半相合移植对WBC、生化和嵌合体的影响；比较供鼠细胞经与不经~(60)Co照射的MHC半相合移植的GVHD情况。结果：供鼠细胞经/不经~(60)Co照射的MHC半相合移植小鼠的肿瘤明显较小,与单纯化疗未进行移植者比较,差异具有统计学意义(P＜0．05)；但受鼠未经化疗预处理的MHC半相合细胞输注没有出现抗肿瘤效应；供鼠细胞经7．5 Gy ~(60)Co照射的MHC半相合移植能明显降低GVHD反应,且对外周血白细胞、生化无不良影响。结论：经7．5 Gy~(60)Co照射的MHC半相合脾加骨髓细胞移植能对H22肝癌细胞产生移植物抗肿瘤效应并降低GVHD反应。     

Indoleamine 2,3‐dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment

Indoleamine 2,3‐dioxygenase (IDO) is a tryptophan‐catabolizing enzyme that has immunoregulatory functions. Our prior study showed that tumoral IDO overexpression is involved in disease progression and impaired patient survival in human ovarian cancer, although its mechanism remains unclear. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. Indoleamine 2,3‐dioxygenase cDNA was transfected into the murine ovarian carcinoma cell line OV2944‐HM‐1, establishing stable clones of IDO‐overexpressing cells (HM‐1‐IDO). Then HM‐1‐IDO or control vector‐transfected cells (HM‐1‐mock) were i.p. transplanted into syngeneic immunocompetent mice. The HM‐1‐IDO‐transplanted mice showed significantly shortened survival compared with HM‐1‐mock‐transplanted (control) mice. On days 11 and 14 following transplantation, the tumor weight of peritoneal dissemination and ascites volume were significantly increased in HM‐1‐IDO‐transplanted mice compared with those of control mice. This tumor‐progressive effect was coincident with significantly reduced numbers of CD8⁺ T cells and natural killer cells within tumors as well as increased levels of transforming growth factor‐β and interleukin‐10 in ascites. Finally, treatment with the IDO inhibitor 1‐methyl‐tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor‐β secretion. These findings showed that tumor‐derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor‐infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity. Therefore, IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.     

树突状细胞在肿瘤中的研究进展

肿瘤的发生、发展与机体免疫状态密切相关。树突状细胞(DCs)是众多免疫细胞中的一种,具有专职抗原提呈功能,在肿瘤免疫过程中发挥关键的调节作用。肿瘤机体中DCs处于异常状态,如成熟障碍、功能异常和表型改变等,无法激活抗肿瘤的特异性免疫反应。目前,基于DCs的肿瘤免疫疗法备受关注,例如通过促进DCs成熟或者利用修饰过的DCs激活机体靶向肿瘤的免疫反应。本文拟对肺癌、结直肠癌、乳腺癌及肝癌等肿瘤中DCs异常相关机制研究以及临床关于DCs疫苗的研究作一综述。