一項在小鼠中的新的研究報告說,，用沙門氏菌治療腫瘤可誘發(fā)一種能夠有效殺滅癌細胞的免疫反應(yīng),。
該發(fā)現(xiàn)可幫助科學(xué)家們創(chuàng)制可注射到病人體內(nèi)的殺滅腫瘤的免疫細胞，或其能證明對研發(fā)一種潛在的抗癌“疫苗”有所幫助,。 在體內(nèi)巡查的免疫細胞常?？蓪⒃缙诘陌┘毎R別為異常的細胞,，并將其殺滅,。 這一過程依賴于連接蛋白43,，這是可在不同類型的細胞間形成細小交通通道（稱作間隙連接）的一種蛋白。 被稱作肽的腫瘤蛋白碎片可通過這些通道逃逸并進入到在其表面展示這些肽的免疫細胞之中,。 這些肽的作用相當于“紅旗警示”,，從而觸發(fā)一種特異性的抗癌免疫反應(yīng)。 但是隨著癌細胞的進展和增殖,，它們可令免疫細胞無法對其進行識別,。 如今,，F(xiàn)abiana Saccheri及其在意大利的同事證明，將沙門氏菌注射到腫瘤之中可令這些腫瘤細胞重新能夠被免疫細胞識別,。 研究人員發(fā)現(xiàn),，被注射的細菌發(fā)揮了一種關(guān)鍵性的功能：它們重新激活了連接蛋白43，而這種蛋白隨著癌細胞的生長常常會受到抑制,。
在本研究中，該團隊發(fā)現(xiàn),，來自小鼠和人的感染了沙門氏菌的黑色素瘤細胞可增加在這些細胞中的連接蛋白43的含量,。 其結(jié)果是新的間隙連接形成了，它使得染有黃色熒光的小分子能夠在腫瘤細胞之間通行或從腫瘤細胞進入免疫細胞,。 但是研究人員希望查明,，這種可使腫瘤肽進入免疫細胞的間隙連接也會在活體動物中出現(xiàn)。 因此,，他們對患癌的小鼠進行了沙門氏菌的治療并觀察到,，正如在實驗室的分離細胞中所觀察到的，這些腫瘤肽可通過間隙連接而進入到免疫細胞之中,，它們在那里被裝載到了細胞的表面,。 這些新被激活的免疫細胞突然能夠識別并殺滅在小鼠中的腫瘤細胞。 令人感興趣的是,，這種方法還保護小鼠不會發(fā)生癌癥擴散到身體的其它部位,，而這正是一種“疫苗接種”形式的預(yù)防性策略。（生物谷Bioon.com）
生物谷近期特別推薦會議：
2010細胞治療研究進展與臨床應(yīng)用前沿研討會 www.Cell-therapies.net 2010年9月23日-25日天津召開
第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國際研討會 www.cancerasia.org 2010年10月12日-10月15日上海召開
生物谷推薦原文出處：
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.
