Researchers found that when they turned cancer cells into immune cells, they were able to teach other immune cells how to attack cancer.
研究人員們發現，當他們將癌細胞轉化成免疫細胞時，它們能使其他免疫細胞學會，如何攻擊癌腫。
Some cities fight gangs with ex-members who educate kids and starve gangs of new recruits. Stanford Medicine researchers have done something similar with cancer — altering cancer cells so that they teach the body’s immune system to fight the very cancer the cells came from.
一些城市具有訓練孩子們，並使新吸收之幫派份子挨餓的打架幫派。史丹佛大學醫學院的研究人員們，已經對癌腫做了類似的事。改變癌細胞，以便它們使身體的免疫系統學會，對抗此些細胞來自之完全一樣的癌腫。
“This approach could open up an entirely new therapeutic approach to treating cancer,” said Ravi Majeti, MD, PhD, a professor of hematology and the study’s senior author. The research was published March 1 in Cancer Discovery. The lead author is Miles Linde, PhD, a former PhD student in immunology who is now at the Fred Hutchinson Cancer Institute in Seattle.
該項研究資深撰文人，血液學教授，Ravi Majeti醫學、哲學博士宣稱：「此方法可能開啟一種，治療癌腫的全新治療方法。」 該項研究(2023年)3 月1日發表於，由美國癌症研究協會出版的《癌症發現》期刊。主要撰文人是，前免疫學博士生，目前於西雅圖市福瑞德·哈金森癌症研究所(Fred Hutchinson Cancer Institute)的Miles Linde博士。
Some of the most promising cancer treatments use the patient’s own immune system to attack the cancer, often by taking the brakes off immune responses to cancer or by teaching the immune system to recognize and attack the cancer more vigorously.
一些最有指望的癌症治療方法，利用病患自身免疫系統來攻擊癌腫，通常藉由採取抑制對癌腫的免疫反應，或藉由使免疫系統學會，更有強有力地識別及攻擊癌腫。
T cells, part of the immune system that learns to identify and attack new pathogens such as viruses, can be trained to recognize specific cancer antigens, which are proteins that generate an immune response.
屬學會識別及攻擊，諸如病毒等新病原體之免疫系統一部分的T細胞，能被訓練來識別，是產生一種免疫反應之蛋白質的特定癌腫抗原。
For instance, in CAR T-cell therapy, T cells are taken from a patient, programmed to recognize a specific cancer antigen, then returned to the patient. But there are many cancer antigens, and physicians sometimes need to guess which ones will be most potent.
譬如，在嵌合抗原受體(CAR：Chimeric antigen receptor) T 細胞的療法中，T 細胞被取自病患，經提供編碼指令序列，來識別特定的癌腫抗原，之後被放回病患體內。不過有很多癌腫抗原，因此醫生們有時需要，猜測哪些是最有效。
A better approach would be to train T cells to recognize cancer via processes that more closely mimic the way things naturally occur in the body — like the way a vaccine teaches the immune system to recognize pathogens.
一種更好的方法是，經由更密切模仿，於身體中自然發生之方式的過程，來使T 細胞學會識別癌腫。就如同疫苗，使免疫系統學會識別病原體的方式。
T cells learn to recognize pathogens because special antigen presenting cells (APCs) gather pieces of the pathogen and show them to the T cells in a way that tells the T cells, “Here is what the pathogen looks like — go get it.”
T 細胞學會識別病原體，因為特殊抗原呈現細胞(APCs)聚集病原體的片段，並以一種告訴 T 細胞的方式，將它們展現給 T 細胞。“這就是病原體呈現給它的樣子”。
Something similar in cancer would be for APCs to gather up the many antigens that characterize a cancer cell. That way, instead of T cells being programmed to attack one or a few antigens, they are trained to recognize many cancer antigens and are more likely to wage a multipronged attack on the cancer.
於癌腫中，對特殊抗原呈現細胞而言，類似的事會是聚集，許多表現出癌細胞特徵的抗原。而那方式，不是T 細胞經提供編碼指令序列，來攻擊一種或幾種抗原。他們經訓練來識別許多癌腫抗原，因此更有可能對癌腫，進行多面性的攻擊。
Now that researchers have become adept at transforming one kind of cell into another, Majeti and his colleagues had a hunch that if they turned cancer cells into a type of APC called macrophages, they would be naturally adept at teaching T cells what to attack.
既然研究人員們已經擅長於，將一種細胞轉化成另一種細胞。Majeti及其同僚有一種，倘若他們將癌細胞轉化成一種，被稱為巨噬細胞的特殊抗原呈現細胞。則它們自然會擅長於，使 T 細胞學會攻擊什麼的預感。
“We hypothesized that maybe cancer cells reprogrammed into macrophage cells could stimulate T cells because those APCs carry all the antigens of the cancer cells they came from,” said Majeti, who is also the RZ Cao Professor, assistant director of the Institute for Stem Cell Biology and Regenerative Medicine and director of the Ludwig Center for Cancer Stem Cell Research and Medicine.
也是幹細胞生物學暨再生醫學研究所副所長、路德維希癌症幹細胞研究暨醫學中心主任之RZ Cao教授的Majeti宣稱：「我們假設，或許癌細胞經重新提供編碼指令序列成為巨噬細胞，能刺激 T 細胞。因為，那些特殊抗原呈現細胞(APC)具有，其來自之癌細胞的所有抗原。」
The study builds on prior research from the Majeti lab showing that cells taken from patients with a type of acute leukemia could be converted into non-leukemic macrophages with many of the properties of APCs.
該研究以來自 先前Majeti 實驗室證實，取自具有一種急性白血病的細胞，能被轉化成具有，諸多特殊抗原呈現細胞屬性之非白血病巨噬細胞的研究為基礎。
In the current study, the researchers programmed mouse leukemia cells so that some of them could be induced to transform themselves into APCs. When they tested their cancer vaccine strategy on the mouse immune system, the mice successfully cleared the cancer.
在目前的研究中，研究人員們對小鼠白血病細胞提供了編碼指令序列，以便其中一些細胞能被誘發，將自身轉化成特殊抗原呈現細胞。當他們針對小鼠免疫系統，測試他們的癌腫疫苗策略時，小鼠成功清除了該癌腫。
“When we first saw the data showing clearance of the leukemia in the mice with working immune systems, we were blown away,” Majeti said. “We couldn’t believe it worked as well as it did.”
Majeti宣稱：「當我們首度看到，在具有作用之免疫系統的此些小鼠中，顯示白血病清除的數據時，被震撼住。我們無法相信，它起了與免疫系統起的一樣作用。」
Other experiments showed that the cells created from cancer cells were indeed acting as antigen-presenting cells that sensitized T cells to the cancer.
其他諸多實驗顯示，從癌細胞產生的細胞確實充當了，使 T 細胞對癌腫敏感之呈現抗原的細胞。
“What’s more, we showed that the immune system remembered what these cells taught them,” Majeti said. “When we reintroduced cancer to these mice over 100 days after the initial tumor inoculation, they still had a strong immunological response that protected them.”
Majeti宣稱：「更重要的是，我們證實，免疫系統記憶了，此些細胞使免疫系統學到什麼。當我們在最初之腫瘤接種疫苗 100 多天後，重新將癌腫引進到此些小鼠時，免疫系統仍然具有保護它們的強烈免疫反應。」
“We wondered, If this works with leukemias, will it also work with solid tumors?” Majeti said. The team tested the same approach using mouse fibrosarcoma, breast cancer, and bone cancer.
Majeti宣稱：「我們很想知道，是否這對白血病起作用，它也會對固態腫瘤起作用？。」該團隊使用小鼠纖維肉瘤、乳腺癌及骨癌，測試了相同的方法。
“The transformation of cancer cells from solid tumors was not as efficient, but we still observed positive results,” Majeti said. With all three cancers, the creation of tumor-derived APCs led to significantly improved survival.
Majeti宣稱：「從固態腫瘤的癌細胞轉化，並非一樣有效。不過，我們仍然觀察到建設性的結果。」對於這三種癌腫，衍生自腫瘤之特殊抗原呈現細胞的產生，顯著導致改善了存活率。
Lastly, the researchers returned to the original type of acute leukemia. When the human leukemia cell-derived APCs were exposed to human T cells from the same patient, they observed all the signs that would be expected if the APCs were indeed teaching the T cells how to attack the leukemia.
最後，此些研究人員返回到原始類型的急性白血病。當此些衍生自人類白血病細胞的特殊抗原呈現細胞，被曝露於來自相同病患的人類 T 細胞時，當此些特殊抗原呈現細胞(APC)確實，使 T 細胞學會如何攻擊白血病時，他們觀察到所有能被預期的跡象。
“We showed that reprogrammed tumor cells could lead to a durable and systemic attack on the cancer in mice and a similar response with human patient immune cells,” Majeti said. “In the future we might be able to take out tumor cells, transform them into APCs and give them back to patients as a therapeutic cancer vaccine.”
Majeti宣稱：「我們證實，重新為腫瘤細胞提供編碼指令序列，能導致對小鼠癌腫持久與系統性的攻擊，及一種對於人類病患免疫細胞的類似反應。於未來，我們或許能取出腫瘤細胞，將它們轉化成特殊抗原呈現細胞，然後作為一種治療性癌腫疫苗，將它們還給病患。」
“Ultimately, we might be able to inject RNA into patients and transform enough cells to activate the immune system against cancer without having to take cells out first,” Majeti said. “That’s science fiction at this point, but that’s the direction we are interested in going.”
Majeti宣稱：「最終，我們或許能將 RNA注入病患體內，且轉化足夠的細胞，來活化免疫系統對抗癌腫，而無需先取出細胞。此時，那是科幻小說。不過，那是我們感興趣致力於的方向。」
網址：https://med.stanford.edu/news/all-news/2023/03/cancer-hematology.html
翻譯：許東榮
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