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分类： 肿瘤治疗 | 修改
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2010-12-28 13:41:55
最潮最好玩的【休闲小游戏】，不玩你就out了
Science
TM：沙门氏菌治疗肿瘤可诱发杀灭癌细胞免疫反应
一项在小鼠中的新的研究报告说，用沙门氏菌治疗肿瘤可诱发一种能够有效杀灭癌细胞的免疫反应。
该发现可帮助科学家们创制可注射到病人体内的杀灭肿瘤的免疫细胞，或其能证明对研发一种潜在的抗癌“疫苗”有所帮助。
在体内巡查的免疫细胞常常可将早期的癌细胞识别为异常的细胞，并将其杀灭。
这一过程依赖于连接蛋白43，这是可在不同类型的细胞间形成细小交通通道（称作间隙连接）的一种蛋白。
被称作肽的肿瘤蛋白碎片可通过这些通道逃逸并进入到在其表面展示这些肽的免疫细胞之中。 这些肽的作用相当于“红旗警示”，从而触发一种特异性的抗癌免疫反应。
但是随着癌细胞的进展和增殖，它们可令免疫细胞无法对其进行识别。 如今，Fabiana
Saccheri及其在意大利的同事证明，将沙门氏菌注射到肿瘤之中可令这些肿瘤细胞重新能够被免疫细胞识别。
研究人员发现，被注射的细菌发挥了一种关键性的功能：它们重新激活了连接蛋白43，而这种蛋白随着癌细胞的生长常常会受到抑制。
在本研究中，该团队发现，来自小鼠和人的感染了沙门氏菌的黑色素瘤细胞可增加在这些细胞中的连接蛋白43的含量。
其结果是新的间隙连接形成了，它使得染有黄色荧光的小分子能够在肿瘤细胞之间通行或从肿瘤细胞进入免疫细胞。
但是研究人员希望查明，这种可使肿瘤肽进入免疫细胞的间隙连接也会在活体动物中出现。
因此，他们对患癌的小鼠进行了沙门氏菌的治疗并观察到，正如在实验室的分离细胞中所观察到的，这些肿瘤肽可通过间隙连接而进入到免疫细胞之中，它们在那里被装载到了细胞的表面。
这些新被激活的免疫细胞突然能够识别并杀灭在小鼠中的肿瘤细胞。
令人感兴趣的是，这种方法还保护小鼠不会发生癌症扩散到身体的其它部位，而这正是一种“疫苗接种”形式的预防性策略。（生物谷Bioon.com）
生物谷近期特别推荐会议：
2010细胞治疗研究进展与临床应用前沿研讨会 www.Cell-therapies.net 2010年9月23日-25日天津召开
第一届肿瘤基础和转化医学国际研讨会 www.
2010年10月12日-10月15日上海召开
生物谷推荐原文出处：
Sci Transl Med DOI:
10.1126/scitranslmed.3000739
Bacteria-Induced Gap Junctions in Tumors
Favor Antigen Cross-Presentation and Antitumor Immunity
Fabiana
Saccheri1, Chiara Pozzi1, Francesca Avogadri2, Sara Barozzi1, Mario Faretta1,
Paola Fusi3 and Maria Rescigno1,*
1Department of Experimental Oncology,
European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy.
2Department of Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York
Avenue, New York, NY 10021, USA.
3Department of Biotechnology and
Biosciences, University of Milano-Bicocca, Milan 20126, Italy.
Antigen-presenting dendritic cells (DCs) trigger the activation of cytotoxic
CD8 T cells that target and eliminate cells with the antigen on their surface.
Although DCs usually pick up and process antigens themselves, they can also
receive peptide antigens from other cells via gap junctions. We demonstrate here
that infection with Salmonella can induce, in both human and murine melanoma
cells, the up-regulation of connexin 43 (Cx43), a ubiquitous protein that forms
gap junctions and that is normally lost during melanoma progression.
Bacteria-treated melanoma cells can establish functional gap junctions with
adjacent DCs. After bacterial infection, these gap junctions transferred
preprocessed antigenic peptides from the tumor cells to the DCs, which then
presented those peptides on their surface. These peptides activated cytotoxic T
cells against the tumor antigen, which could control the growth of distant
uninfected tumors. Melanoma cells in which Cx43 had been silenced, when infected
in vivo with bacteria, failed to elicit a cytotoxic antitumor response,
indicating that this Cx43 mechanism is the principal one used in vivo for the
generation of antitumor responses. The Cx43-dependent cross-presentation pathway
is more effective than standard protocols of DC loading (peptide, tumor lysates,
or apoptotic bodies) for generating DC-based tumor vaccines that both inhibit
existing tumors and prevent tumor establishment. In conclusion, we exploited an
antimicrobial response present in tumor cells to activate cytotoxic CD8 T cells
specific for tumor-generated peptides that could directly recognize and kill
tumor cells.
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