重编程技术可使肿瘤细胞自我毁灭

Norris Cotton 癌症研究中心和Geisel医学院的研究员发现，插入特定的细菌片段到具有攻击性的卵巢癌微环境中，可将肿瘤细胞的活性从抑制性转变为免疫刺激性。这一发现发表在《肿瘤免疫学》杂志上,文章表明免疫治疗的新方法可以应用于各种各样的癌症类型中。

“通过引入一种具有弱毒性和安全性的细菌（单核细胞增多性李斯特氏菌(Lm)），通过与Aduro生物科技有限公司合作我们发现减毒细菌被免疫抑制细胞吸收，并且将免疫抑制细胞从保护肿瘤的细胞转变为攻击肿瘤的细胞。”Steve Fiering博士说,他是这项研究的主要作者。

肿瘤通过免疫系统产生的免疫抑制微环境来保护自己免受攻击。研究的结果发现，单核细胞增多性李斯特氏菌对增加促炎细胞因子和趋化因子具有非常大的作用,并且可以补充免疫效应细胞的亚型,支持抗肿瘤免疫力。改变免疫抑制肿瘤微环境是一个可行方法,这种方法可以结合其它免疫依赖性的治疗方法来治疗其他癌症如卵巢癌。

“调节肿瘤微环境可把免疫抑制吞噬细胞变为抗肿瘤免疫应答细胞，这项实验早在一百年前就已由William Coley博士完成。”Fiering说。“既然我们可以改变微生物,使它们可以安全的使用,也可以追踪详细的抗肿瘤免疫反应过程,那么它可能有潜在的治疗癌症的可行性。”

Aduro生物技术公司开发的单核细胞增多性李斯特氏菌减毒株,已经在临床试验中用于治疗胰腺癌。“我们将进一步研究机制以及探索在癌症治疗中如何使用这种方法,并将支持未来的治疗卵巢癌的临床试验。“Fiering说。（转化医学网360zhyx.com）

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原文：Inserting a specific strain of bacteria into the microenvironment of aggressive ovarian cancer transforms the behavior of tumor cells from suppression to immunostimulation, researchers at Norris Cotton Cancer Center and the Geisel School of Medicine have found. The findings, published in OncoImmunology, demonstrate a new approach in immunotherapy that can be applied in a variety of cancer types.

"By introducing an attenuated and safe form of the bacteria Listeria monocytogenes (Lm), in collaboration with Aduro Biotech Inc., we found that the attenuated bacteria is taken up by the immunosuppressive cells and transforms them from cells that protect the tumor into cells that attack the tumor," said Steve Fiering, PhD, lead author of the study.

Tumors protect themselves from attack by the immune system by generating an immunosuppressive microenvironment. The study's results found that Lm has a significant impact in increasing the amount of pro-inflammatory cytokines and chemokines, and recruiting immune effector cell subsets, that strongly support anti-tumor immunity. Modifying the immunosuppressive tumor microenvironment remains an approach that can be combined with other immune-based treatment to treat other cancers in addition to ovarian cancer.

"Modulation of the tumor microenvironment to make the immunosuppressive phagocytes into cells that support anti-tumor immune responses has roots in experiments done a hundred years ago by Dr. William Coley," Fiering said. "Now that we can engineer microorganisms to make them safe to use and also can track the anti-tumor immune response in great detail, it has new potential for use in cancer treatment."

The attenuated strain of Lm, developed by Aduro Biotech Inc., is already in clinical trials for the treatment of pancreatic cancer. "Our studies provide further understanding of the mechanisms involved and how this approach can be used in cancer treatment, and will support future clinical trials for treatment of ovarian cancer," Fiering said.