叉头样转录因子3在肺恶性肿瘤中的作用

叉头样转录因子（Foxp3）是一个具有多种功能的转录因子,通常调控细胞生长发育,不但在肿瘤发生、发展中发挥作用,而且在肿瘤的治疗、预后评估中均起着相当重要的作用.Foxp3是通过调控调节性T细胞（Treg细胞）水平,抑制肿瘤微环境免疫功能,使肿瘤细胞逃避免疫监视,导致肿瘤的发生.抑制Foxp3表达,使机体发挥正常免疫功能,可达到抗肿瘤目的.本文就Foxp3在肺恶性肿瘤中的表达和肿瘤免疫中的作用机制以及免疫治疗中的作用作一综述.     

SEL1L分子及内质网相关降解途径在肿瘤进展中的作用

lin-12-like抑制/增强子(suppressor /enhancer of lin-12-like, SEL1L)分子可以参与调控多种肿瘤进展;同时,其作为内质网相关降解途径(endoplasmic reticulum -associated degradation,ERAD)的重要组成,还参与调控蛋白质合成,与内质网应激(ER stress)及其引起的未折叠蛋白反应(unfolded protein response,UPR)密切相关。在肿瘤微环境中,ERAD不仅参与调控肿瘤细胞的生物学行为,对肿瘤进展发挥重要作用;其还参与对免疫细胞增殖分化、功能以及代谢途径的调节,影响免疫细胞发挥抗肿瘤免疫作用。因此,深入了解探索肿瘤微环境中SEL1L分子及ERAD的潜在机制,可为肿瘤发生、发展及免疫治疗提供新理论和新靶点。本文就SEL1L分子及其参与的内质网相关降解途径在肿瘤进展与免疫调节中的作用进行简要综述。     

TGF-β在肿瘤免疫微环境中的作用及研究进展

肿瘤免疫微环境被视为肿瘤"第七大标记性特征",肿瘤免疫逃逸与肿瘤发生和转移密切相关。作为肿瘤免疫逃逸的主要调控因子,TGF-β可抑制多种免疫细胞在肿瘤组织中增殖分化,表现为诱导肿瘤相关巨噬细胞和TAN极化,阻断树突状细胞的成熟,促进调节性T细胞的产生,还可以募集髓系抑制性细胞,加强TGF-β信号在肿瘤微环境中的促癌作用。因此抑制TGF-β的功能,重建抗肿瘤免疫环境将成为治疗肿瘤的一个重要策略。本文对TGF-β在肿瘤免疫微环境中的相关作用及研究进展进行综述。     

中医药调节肿瘤免疫微环境研究进展

肿瘤的发生发展与肿瘤免疫微环境密切相关。在肿瘤的形成过程中,肿瘤免疫微环境不仅能够促进肿瘤的发生发展,也能够抑制肿瘤的发生发展。中医药对肿瘤免疫微环境中的细胞毒性T细胞、自然杀伤细胞、树突状细胞、IL-12有正向调节作用,对肿瘤免疫微环境中的调节性T细胞、肿瘤相关巨噬细胞、髓系来源的抑制性细胞、PD-1/PD-L1有负向调节作用。应重视中医药调节肿瘤免疫微环境的作用机制研究。     

当归及其活性成分对肿瘤微环境免疫功能的影响及其抗肿瘤作用机制研究概况

肿瘤微环境为肿瘤细胞的增殖、侵袭和转移等恶性生物学行为提供了"肥沃土壤"。当归及其有效活性成分(当归多糖APS,当归内酯ASDL)具有抗肿瘤的药效学基础,能够靶向肿瘤微环境,通过增强免疫器官免疫功能,提升免疫细胞和免疫因子的活性,达到间接抗肿瘤的目的。同时,当归具有抑制肿瘤生长,诱导细胞凋亡,减轻化疗毒副作用,减少细胞损伤及阻断和调控肿瘤细胞信息通路等抗肿瘤药理活性,从而发挥抗肿瘤作用。     

放疗联合免疫检查点抑制剂的研究进展

近期免疫检查点抑制剂成为癌症治疗的主流,在免疫治疗期间接受放疗的患者中观察到远隔效应。放疗可诱导或提高抗肿瘤免疫,使抗肿瘤治疗取得重大突破。放疗还可引起免疫源性细胞死亡,并可促进肿瘤微环境中T细胞的募集及其功能。放疗协同免疫检查点抑制剂恢复了抗肿瘤T细胞的活性剂功能,该协同作用显著提高了治疗效果,使存在抗肿瘤免疫的患者获益。     

线粒体调控肿瘤免疫的研究进展

肿瘤细胞通过改变自身代谢以适应能量和生物合成的需求。线粒体作为肿瘤细胞代谢重编程的关键细胞器,其功能异常是癌症发生和进展的主要驱动因素。线粒体动力学和能量代谢途径的改变对免疫细胞活化、增殖和分化至关重要,肿瘤微环境通过诱导免疫细胞线粒体代谢重编程和线粒体动力学变化,影响肿瘤浸润免疫细胞的活化和功能,进而促进肿瘤免疫抑制微环境形成;线粒体应激介导的线粒体DNA泄露可通过激活多条天然免疫信号通路,如cGAS-STING、TLR9和NLRP3,在宿主抗肿瘤免疫响应和肿瘤免疫抑制微环境的塑造中扮演复杂的调控角色,线粒体DNA介导的免疫原性细胞死亡是目前极具潜力的抗肿瘤免疫治疗手段;线粒体活性氧作为肿瘤发生的重要媒介,通过改变肿瘤微环境中免疫细胞组成,推动肿瘤免疫抑制微环境形成。本文围绕线粒体生物学与抗肿瘤免疫应答之间的关系,从多个角度探讨线粒体在肿瘤-宿主互作中的核心作用,以期为开发靶向线粒体的抗肿瘤免疫治疗策略提供参考。     

姜黄素调控抗肿瘤相关细胞转录因子及信号转导通路的研究进展

姜黄素是姜黄根茎提取活性成分,具有抗炎、抗凝、抗氧化,降血脂和抗肿瘤特性。近年来姜黄素的抗肿瘤作用逐渐成为研究热点之一。姜黄素可抑制在肿瘤的发生和发展中起着关键作用的细胞核转录因子-κB(NF-κB)和STAT蛋白抑制因子3(STAT3)信号通路。同时,对蛋白转录因子SP-1和管家基因表达的抑制作用可防止肿瘤的形成,迁移和侵袭。最近研究还发现,内质网应激和自噬在细胞凋亡过程中发挥作用,而抑制自噬可增加姜黄素及类似物介导的内质网应激,从而进一步诱导细胞凋亡。现就姜黄素通过调控转录因子及内质网应激与自噬信号通路诱导肿瘤细胞的凋亡和抗血管生成的抗肿瘤作用机制作如下综述。     

肿瘤浸润性T细胞代谢重组及功能的研究进展

［摘要］ 代谢重组是肿瘤细胞维持活力和功能的必要条件,同时也是调控肿瘤免疫逃逸的关键因素。在肿瘤微环境中,除了通过抑制配体直接影响T细胞的生理功能外,肿瘤细胞还通过代谢重组影响T细胞代谢进而对其进行免疫调节。而对于肿瘤浸润性T细胞而言,在通过改变代谢模式适应肿瘤局部营养环境的同时,其免疫功能亦发生变化,具体体现在免疫监视功能减弱,甚至促进肿瘤生长和转移。近年来,肿瘤组织中免疫细胞的代谢研究一直是肿瘤免疫学界的热点话题,本文主要就肿瘤微环境中肿瘤细胞与肿瘤浸润性T细胞之间基于代谢重组的交互作用进行综述,在梳理既往研究的同时,为今后的相关研究提供方向。     

调节性T细胞与肿瘤相互作用机制的研究进展

近年来恶性肿瘤发病率呈逐年上升趋势,严重威胁着人类的健康和生存质量。肿瘤的发生、发展与机体的免疫状态密切相关。调节性T(Treg)细胞因其特殊的免疫调节作用成为肿瘤免疫学领域的研究热点之一,引起了国内外学者前所未有的重视。目前研究陆续发现各种恶性肿瘤患者外周血及肿瘤微环境中Treg细胞比例增加,去除Treg细胞或封闭其抑制功能可以增强抗肿瘤免疫反应。Treg细胞在肿瘤微环境中的产生方式和抑制机制均呈现多样化。     

Targeting Foxp3+ regulatory T cells-related immunosuppression for cancer immunotherapy

Objective To review the current research into Foxp3^＋ regulatory T cells （Treg） cell surface molecules, plasticity of Treg cells and mechanisms of Treg cell suppression and to explore the possibilities to interfere in Treg cell suppression of anti-tumor immunity. Data sources A literature search of all English articles was performed on the online electronic PubMed database dated 1995 to 2010. The keywords searched included： CD4^＋CD25^＋Foxp3^＋ regulatory T lymphocytes, cancer, and immunotherapy. After finding relevant articles within these search limits, a manual search was conducted through the references from these articles. Study selection Articles regarding the role of Treg cells in tumor immunity and the utility of Treg cells in tumor immunotherapy. Results The results show that significant numbers of Treg cells are found in many tumors and it has been shown that the number of tumor infiltrating Treg cells correlates with adverse clinic outcomes. Treg cells are emerging as a key component of acquired tolerance to tumors. Conclusions Several mechanisms of immunosuppression can be mediated by Treg cell function. Distinct immunosuppressive molecules expressed by Treg cells or diverse molecules related to Treg induction or migration represent potential drug targets for caner immunotherapy.     

CD4~+CD25~+调节性T细胞在肿瘤免疫中的研究进展

调节性T细胞(regulatory T cells,Treg细胞)是一类控制体内自身免疫反应的具有免疫抑制功能的T细胞亚群,与自身免疫性疾病的发生、移植耐受、肿瘤的免疫抑制等关系密切。近年来,Treg细胞在肿瘤中的作用研究逐渐成为热点,受到广泛关注。研究发现Treg细胞在肿瘤的发生、发展和转移的过程中发挥重要作用,可通过细胞-细胞接触、分泌抑制性细胞因子、干扰细胞代谢等方式直接或间接影响CD4~+CD8~+效应T细胞的功能,从而抑制机体的抗肿瘤免疫。因此,针对Treg的免疫疗法对于治疗肿瘤具有广阔前景。本文就调节性T细胞的作用机制特点及其与肿瘤免疫的关系做一简要综述。     

Effect of Diallyl Trisulfide on the Activation of T Cell and Macrophage－mediated Cytotoxicity

(冯作化)(张桂梅)(郝天玲)(周斌)(张慧)(姜志尧)ＥｆｆｅｃｔｏｆＤｉａｌｌｙｌＴｒｉｓｕｌｆｉｄｅｏｎｔｈｅＡｃｔｉｖａｔｉｏｎｏｆＴＣｅｌｌａｎｄＭａｃｒｏｐｈａｇｅ－ｍｅｄｉａｔｅｄＣｙｔｏｔｏｘｉｃｉｔｙ￥ＦＥＮＧＺｕｏ－ｈｕａ；ＺＨＡＮＧＧｕｉ－...     

Antitumor effects of the fibroblasts transfected TNF-α gene and its mutants

Summary To compare the anti-tumor effects of transmembrane TNF-α (TM-TNF) and secreted TNF-α (S-TNF)in vivo, mouse fibroblasts NIH3T3 were transfected separately with three types of retrovirus containing wild type TNF-α (Wt-TNF), TM-TNF mutant (TM-TNFm), S-TNF mutant (S-TNFm). Southern blot, RT-PCR, FACS and bioassay were used to investigate TNF-α gene integration, expression and its biological activity. It was found that both fixed cells and supernatant of NIH3T3/Wt-TNF, the fixed cells of NIH3T3/TM-TNFm and the supernatant of NIH3T3/S-TNFm could express high level of TNF-α or its mutants and effectively kill H22in vitro. The trans-fected NIH3T3 were separately injected into the mice at the sites of H22 tumor cell inoculation according to a ratio of 5∶1 or 1∶1 (effector/target cells, E/T) after the third day of H22 challenge, respectively. At the E/T=5∶1, the NIH3T3/TM-TNFm induced the highest tumor regression, while NIH3T3/S-TNFm exerted the strongest tumor depressing effect at the E/T=1∶1in vivo. No obvious side effects were noted throughout the course of treatment. The results suggest that both TM-TNF and S-TNF could cause tumor regression. The anti-tumor effect of TM-TNF would be more powerful and safe than that of S-TNF at the proper E/T ratio. LI Qingfen, female, born in 1965, Associate Professor     

1-MT enhances potency of tumor cell lysate-pulsed dendritic cells against pancreatic adenocarcinoma by downregulating the percentage of tregs

This study examined whether 1-methyl-tryptophan [1-MT,an indoleamine 2,3-dioxygenase(IDO) inhibitor] could reduce CD4+CD25+ regulatory T cells(Tregs) proliferation and improve the anti-tumor efficacy of dendritic cells(DCs) pulsed with tumor cell lysate in the mice bearing pancreatic adenocarcinoma.The models of pancreatic adenocarcinoma were established in C57BL/6 mice by subcutaneous injection of Pan02 cells.Eight mice which were subcutaneously injected with PBS served as control.The expression of IDO was...     

PD-1/PD-L1信号通路及其在肿瘤免疫治疗中的作用

抑制性共刺激分子程序性死亡因子1(PD-1)/程序性死亡因子配体1(PD-L1)是重要的负性免疫调节分子,在机体适应性细胞免疫中发挥着重要作用.表达PD-L1的肿瘤细胞可与T细胞表面受体分子PD-1特异性结合,从而影响T细胞的活化与分化,并抑制T细胞的抗肿瘤免疫杀伤活性.目前,已有多种靶向PD-1/PD-L1免疫检查点的药物应用于临床,并在不同类型的肿瘤治疗中显示出良好疗效.本文就PD-1/PD-L1的分子结构、表达特点、上调影响因素,以及其在促进肿瘤生长、免疫逃逸、肿瘤免疫治疗中的作用等方面的研究进展作一综述.     

STUDY ON THE ANTI—TUMOR EFFICACY INDUCED BY HEAT SHOCK PROTEIN 70—PEPTIDE COMPLEXES DERIVED FROM TUMOR CELLS

Heatshockprotein７０（HSP７０）derivedfromtumocellscouldelicitstronganti－tumorimmunity（１，２）．IcarriesmultipletumorantigenicpeptidescalledHSP７０－peptidecomplexes（HSP７０－PC）．HSP７０chaper－oningtumorantigenicpeptideisexpressedontumorcellmembran     

Anti-tumor Effect and Mechanism of SEA-Fab＇ Coupled Protein on Gastric Tumor

Summary The anti-tumor effect and mechanism of SEA-Fab' coupled protein on gastric tumor was studied. The target cell Walker-256 was treated with SEA-Fab' synthesized chemically or SEA respectively for 24 h, 36 h or 72 h. PBMC+Walke-256 cells served as controls. The apoptotic index of SEA-Fab' against effector cells was detected. In the mouse gastric cancer models (n=60), SEA-Fab', SEA and normal saline was injected in experimental group, SEA group and control group respectively. The occurrence and weight of tumor was observed. The results showed that the apoptotic index was significantly higher in the SEA-Fab' (34.6%–68.9%) and SEA group (15.5%–31.9%) than in PBMC+Walker-256 group (5.5%–12.8%) with the difference being significant (P<0.01). And there was significant difference between SEA-Fab' group and SEA group (P <0.01). The tumor weight in SEA-Fab', SEA and control groups was 3.64±0.53 g, 0.78±0.26 g and 0.49±0.17 g respectively with the difference being statistically significant between the SEA-Fab' group, SEA group and the control group (P<0.01). In the SEA-Fab's and SEA groups, there were CD4⁺ T and CD8⁺ T cell infiltrates, but in the control group, no or few T lymphocytes were seen in the mouse tumor tissue. It was concluded that SEA-Fab' was more effective to activate T lymphocytes to kill the tumor cells than SEA used alone. It was feasibility by using the monoclonal antibody as carrier to perform the targeted immunotherapy of gatric tumor. SHU Xiaogang, male, born in 1971, Doctor in Charge, M. D., Ph. D.