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乳腺瘤微生物组调节抗瘤免疫和T细胞相关代谢物

Chin-Chih Liu¹, Dennis Grencewicz², Karthik Chakravarthy³

¹Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

bioRxiv : the preprint server for biology

|November 18, 2024

概括

乳腺瘤微生物组,特别是葡萄球菌,与CD8+ T细胞相关,并影响代谢物. 葡萄球菌激活CD8+T细胞可能提供新的乳腺癌免疫治疗策略.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
微生物组研究微生物组研究

背景情况:

乳腺癌是女性最常见的癌症,其瘤微生物组在宿主生物学中的作用尚不清楚.
CD8+瘤透淋巴细胞 (TILs) 对抗瘤免疫至关重要,影响癌症预后和治疗反应.
了解瘤微生物群,代谢物和CD8+TIL之间的相互作用,对于推进乳腺癌疗法至关重要.

研究的目的:

研究CD8+TILs,乳腺瘤微生物组和代谢组之间的相互作用.
确定乳腺瘤微生物组如何影响瘤代谢和抗瘤免疫.
探索针对瘤微生物组进行乳腺癌免疫治疗的潜力.

主要方法:

分析了46名乳腺癌患者 (A组) 的瘤代谢和CD8+TILs,使用质谱和免疫组织化学.
从以前的16S rRNA测序和mRNA表达面板数据中特征化了微生物组组成和T细胞基因表达.
在370名患者 (B队列) 中检查了葡萄球菌-乳腺癌亚型相互作用,并在TNBC小鼠模型中探索了微生物组功能.

主要成果:

葡萄球菌的丰富性与A队列的T细胞激活基因具有积极的相关性.
在Staphylococcus阳性和阴性瘤之间,特定代谢物 (NADH,γ-glutamyltryptophan,γ-glutamylglutamate) 不同.
在小鼠模型中,内葡萄球菌,特别是金黄色葡萄球菌,激活了CD8+TILs,耗尽了NAD代谢物,并减少了TNBC瘤的生长.

结论:

确定了与乳腺瘤中CD8+TILs相关的关键代谢物和微生物种类.
描述了瘤微生物组和代谢组之间的相互作用,表明葡萄球菌会影响抗瘤免疫力.
研究结果表明,低生物质微生物在瘤中起作用,为乳腺癌免疫治疗提供了潜在的生物标志物和治疗点.

关键词:

微生物组是一个微生物组.黄金色的S. 黄金色的这种病原体是葡萄球菌.在T细胞,T细胞.抗瘤免疫力抗瘤免疫力乳腺癌乳腺癌乳腺癌代谢代谢代谢代谢代谢组代谢组的代谢瘤微环境是一个微环境.透到瘤中的淋巴细胞

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