Good News About a Very Bad Cancer
by Mitch Leslie 胡德良 译
一个胰腺癌肿瘤散到肝脏中（见左图），病人在接受化疗并摄入一种刺激巨噬细胞的抗体之后，肿瘤消失了（见右图）。
| Pancreatic cancer is relentless and typically kills patients within a few months. Now scientists report that a treatment that fires up certain immune cells extends the lives of pancreatic cancer patients by more than 30%. Although the recipients survived for only about an extra 2 months, cancer researchers are enthusiastic about the results. | 胰腺癌是无情的，通常几个月之内就能致病人于死地。现在科学家们报道说，一种刺激某类免疫细胞的疗法可以将胰腺癌病人的生命延长30%以上。尽管接受治疗者的生命仅仅延长了大约2个月，但是癌症研究人员仍然对这个效果满怀热情。 |
| The statistics on pancreatic cancer are dismal. Only about 5% of patients with pancreatic ductal adenocarcinoma (PDA), the most common form of the disease, are alive 5 years after diagnosis. And the odds of beating pancreatic cancer haven't improved much in the past 35 years, notes surgeon and cancer researcher Jason Fleming of MD Anderson Cancer Center in Houston, Texas. "We are really at square one with survival," he says. | 胰腺癌的统计资料是可怕的：只有大约5%的胰腺导管癌（PDA）病人在确诊后能够存活5年时间。PDA是胰腺癌中最常见的一种。德克萨斯州休斯顿市MD安德森癌症中心的外科医生兼癌症研究人员詹森·弗莱明指出：过去的35年中，在对抗胰腺癌方面并没有取得大幅度的进展。“在病人的存活时间问题上，我们真正需要从零开始。” |
| One of pancreatic cancer's dirty tricks involves co-opting white blood cells called leukocytes. Instead of attacking, these turncoats infiltrate the cancer and "essentially wall it off from the antitumor effects of the immune system," says tumor immunologist Robert Vonderheide of the University of Pennsylvania's Abramson Cancer Center. Vonderheide and colleagues wondered whether they could turn the immune system against the cancer by triggering CD40, a receptor protein carried by several kinds of defensive cells. Activating CD40 is usually necessary for immune cells to take on tumors. | 胰腺肿瘤一个讨厌的把戏是吸收白细胞（leukocytes）。宾夕法尼亚大学亚伯拉姆森癌症中心的肿瘤免疫学家罗伯特·冯德海德说：这些叛变的细胞并不进行抗击，相反它们渗入到肿瘤中，“从根本上阻挡了免疫系统的抗肿瘤作用。”冯德海德及同事想搞清楚，能否通过启动几种防御性细胞所携带的蛋白受体CD40来使免疫系统对抗这种癌症。为了使免疫细胞对抗肿瘤，通常有必要激活CD40受体。 |
| The researchers dosed 21 PDA patients with the standard chemotherapy drug gemcitabine and an antibody that flips on CD40. Computed tomography scans showed that pancreatic tumors dwindled or stabilized in 15 of the subjects. In some of the recipients, the treatment also shrank metastatic tumors, or colonies from the original cancer that had sprouted in other parts of the body. Historically, PDA patients who receive gemcitabine survive about 5.7 months. But as the researchers report online today in Science, patients in the experimental group lived for 7.4 months. | 研究人员让21个PDA患者摄入标准剂量的化疗药物——吉西他滨，并且给他们服用刺激CD40受体的一种抗体。计算机断层扫描显示，15个接受治疗的病人中，胰腺肿瘤有的缩小了，有的保持在稳定状态。在一些病人中，该疗法还使转移瘤缩小了。转移瘤是指源自原始肿瘤并在身体其他部位萌发的肿瘤群。从历史上来讲，那些接收吉西他滨治疗的PDA病人存活时间约为5.7个月。然而，研究人员今天在《科学》杂志在线版上报道说，实验组的病人们存活了7.4个月。 |
| To determine how the treatment curbed tumor growth, the researchers tested genetically engineered mice that develop PDA. The combination of gemcitabine and a rodent version of the CD40-activating antibody—and even the mouse antibody alone—reduced tumors in about 30% of the animals. The researchers expected that activating CD40 would provoke a counterattack by the immune cells known as T cells. But to their surprise, they found that the antibody worked even in mice that lack these cells. Instead, the attackers were macrophages, a more general kind of defensive cell whose jobs include munching bacterial invaders and helping to heal injured tissue. Macrophages were able to squirm through the white blood cell blockade and start killing the tumor cells. | 为了确定这种疗法是如何抑制肿瘤生长的，研究人员拿患有PDA的基因工程小鼠做试验。将吉西他滨和啮齿动物型CD40激活抗体结合起来使用，甚至仅仅使用啮齿动物型抗体，就使小鼠的肿瘤减小了大约30%。研究人员期望通过刺激CD40受体将会引起一种叫做“T细胞”的免疫细胞进行反击。然而令他们感到吃惊的是，这种抗体甚至在没有T细胞的小鼠体内也能够起作用，因为发起攻击的细胞竟然是巨噬细胞。巨噬细胞是一种更为广泛存在的防御性细胞，其任务包括吞噬入侵细菌和帮助受伤组织愈合。巨噬细胞能够蠕动着穿透白细胞的封锁，进而杀死肿瘤细胞。 |
| "These are promising results that need to be expanded and tested further in larger studies," says Vonderheide. One question to investigate, he says, is whether other combinations of treatments boost the activator's killing power, such as pairing it with a vaccine that incites T cells to attack the tumor. | “这些成果是很有希望的，值得推广，同时也需要进一步在较为大型的研究中进行试验，”冯德海德说。他表示，一个需要研究的问题是，其他类型的复合疗法是否可以提高这种激活剂的杀伤力，例如，为它配上一种引起T细胞攻击肿瘤的疫苗。 |
| Cancer experts are impressed. "It's a great article," says Fleming. "It's definitely a huge step forward," adds cancer biologist Dafna Bar-Sagi of the New York University School of Medicine in New York City. Stretching survival by less than 2 months might not seem like a big deal, but given the poor prognosis for most patients, "these are significant numbers," says molecular biologist Jonathan Brody of Thomas Jefferson University in Philadelphia, Pennsylvania. All three researchers, who were not involved in the study, agree that the results highlight the importance of designing treatments that focus not just on tumor cells but also on the neighboring tissue that helps them survive and grow. "We need to be targeting those cells," Brody says. | 癌症专家们深受感动。“这是一篇很棒的论文，”弗莱明说。纽约大学医学院的肿瘤生物学家达夫纳·巴萨吉接着说：“无疑，这等于向前跨出了一大步。”宾夕法尼亚州费城市托马斯杰斐逊大学的分子生物学家乔纳森·布罗迪说：将病人的存活时间延长了不到两个月，可能听起来好像不是一个多么大的事情，但是鉴于多数病人的不良预后，“这些数字的意义是重大的。”所有的这三个研究人员都没有参与这项研究，但他们一致同意这些研究成果突出了设计治疗方案的重要性，即：在设计治疗方案时不能仅仅把注意力集中在肿瘤细胞上，还要注意有助于肿瘤细胞存活和生长的周围组织。“我们需要把目标指向周围的细胞，”布罗迪说。 |
译自：美国《科学》杂志网站（24 March 2011, 2:01 PM）
原著：Mitch Leslie
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