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Nutrient found in beef and dairy improves immune response to cancer: Study
《自然》雜志：研究發現牛羊肉中營養素可提高癌癥治療效果
The study shows that patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting that it could have potential as a nutritional supplement to complement clinical treatments for cancer.
研究顯示，血液中TVA水平較高的患者對免疫治療的反應更好，這表明TVA可能作為一種營養補充劑，作為臨床治療癌癥的輔助方法。
"There are many studies trying to decipher the link between diet and human health, and it's very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology," said Jing Chen, Ph.D., the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the study.
“有許多研究試圖解密飲食與人類健康之間的聯系，但由于人們吃的食物種類繁多，要理解其背后的機制非常困難。但如果我們只關注食物中的營養物質和代謝產物，我們就開始看到它們是如何影響生理和病理的”，芝加哥大學醫學院珍妮特·戴維森·羅利杰出服務教授、本研究論文的主要作者陳靖博士說。
"By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumor immunity by activating an important immune pathway."
“通過重點研究能激活 T 細胞反應的營養素，我們發現了一種營養素，它能通過激活一條重要的免疫途徑來增強抗腫瘤免疫力?！?/p>
Chen's lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments.
陳靖團隊專注于研究血液中的代謝物、營養素和其他分子是如何影響癌癥的發展和對癌癥治療的反應。
For the new study, two postdoctoral fellows, Hao Fan, Ph.D. and Siyuan Xia, Ph.D., both co-first authors, started with a database of around 700 known metabolites that come from food and assembled a "blood nutrient" compound library consisting of 235 bioactive molecules derived from nutrients.
兩位博士后研究員范浩和夏思源都是該項最新研究的共同第一作者，他們從大約700種已知的食物來源的代謝物中篩選出了235種具有生物活性的分子，組成了一個“血液營養物質”化合物庫。
They screened the compounds in this new library for their ability to influence anti-tumor immunity by activating CD8+ T cells, a group of immune cells critical for killing cancerous or virally-infected cells.
研究人員篩選了這個新化合物庫中的化合物，以了解它們通過激活CD8+ T細胞來影響抗腫瘤免疫的能力，CD8+ T細胞是對殺死癌變或病毒感染的細胞至關重要的免疫細胞。
After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. "That means there must be something else it does, so we started working on it more," Chen said.
在對人類和小鼠細胞進行了六種候選分子的評估后，科學家們發現TVA的表現最好。TVA是母乳中最豐富的反式脂肪酸，但人體無法自己合成。只有大約20%的TVA被分解成其他的副產品，剩下的80%在血液中循環。“這意味著它一定還有其他作用，所以我們開始對其進一步研究”，陳靖說。
The researchers then conducted a series of experiments with cells and mouse models of diverse tumor types. Feeding mice a diet enriched with TVA significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumors.
研究人員隨后用不同腫瘤類型的細胞和小鼠模型進行了一系列實驗。與喂食對照飲食的小鼠相比，喂食富含TVA的飲食能顯著降低小鼠黑色素瘤和結腸癌細胞的腫瘤生長潛能。TVA 飲食還能增強 CD8+ T 細胞浸潤腫瘤的能力。
The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, Ph.D., the John T. Wilson Distinguished Service Professor of Chemistry at UChicago and another senior author of the study.
該團隊還進行了一系列的分子和遺傳分析，以了解TVA是如何影響T細胞的。這些分析包括一種用于監測單鏈DNA轉錄的新技術，稱為酮戊二醛輔助單鏈DNA測序，或KAS-seq，由芝加哥大學化學系約翰·T·威爾遜杰出服務教授、本研究的另一位主要作者何川博士開發。
These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation.
陳靖和何川的實驗室完成的這些實驗顯示TVA能夠使細胞表面的一種受體失活，這種受體叫做GPR43，通常被腸道菌群產生的短鏈脂肪酸激活。TVA壓制了這些短鏈脂肪酸，激活了一種稱為CREB通路的細胞信號過程，CREB通路參與多種功能，包括細胞的生長、存活和分化。
The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumor fighting ability.
研究團隊還發現，CD8+ T 細胞中的 GPR43 受體被完全清除的小鼠模型也無法提高抗腫瘤能力。
Finally, the team also worked with Justin Kline, MD, Professor of Medicine at UChicago, to analyze blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma.
最后，研究小組還與芝加哥大學醫學教授、醫學博士賈斯汀·克萊恩合作，對接受CAR-T細胞免疫療法治療的淋巴瘤患者的血液樣本進行了分析。
They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested cell lines from leukemia by working with Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine, and saw that TVA enhanced the ability of an immunotherapy drug to kill leukemia cells.
他們發現，TVA水平較高的患者往往比TVA水平較低的患者對治療的反應更好。他們還與 醫學教授Anjuli Seth Nayak、醫學博士溫迪·施托克合作測試了白血病細胞系，發現 TVA 增強了免疫療法藥物殺死白血病細胞的能力。
來源：medicalxperss
編輯：董靜
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