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作者：SCI天天读
SCI
15 May 2024
A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron
(Nature Immunology, IF: 30.5)
Garima Sharma, Amit Sharma, Inhae Kim, Dong Gon Cha, Somi Kim, Eun Seo Park, Jae Gyun Noh, Juhee Lee, Ja Hyeon Ku, Yoon Ha Choi, JungHo Kong, Haena Lee, Haeun Ko, Juhun Lee, Anna Notaro, Seol Hee Hong, Joon Haeng Rhee, Sang Geon Kim, Cristina De Castro, Antonio Molinaro, Kunyoo Shin, Sanguk Kim, Jong Kyoung Kim, Dipayan Rudra, Sin-Hyeog Im
CORRESPONDENCE TO: drudra@shanghaitech.edu.cn; iimsh@postech.ac.kr
Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8+ T cell response, and triggers macrophage ‘nutritional immunity’ to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into ‘oncobiotics’ for a multi-layered approach to cancer therapy.
天然免疫细胞可产生多方面的抗肿瘤免疫反应，例如保存铁等必需营养素。这些天然免疫细胞可以被共生细菌调节；然而，识别和理解这种情况是如何发生的是一个挑战。在这里，我们发现食物共生植物乳杆菌IMB19在同基因和异种移植小鼠肿瘤模型中增强抗肿瘤免疫。其荚膜杂多糖是主要的效应分子，可作TLR2配体。共生植物乳杆菌IMB19以双管齐下的方式将肿瘤相关巨噬细胞偏移为经典的活性表型，促使产生持续的CD8+T细胞反应，并触发巨噬细胞的“营养免疫”，以部署高亲和力铁转运蛋白Lipocalin-2-2，在肿瘤微环境中捕获和螯合铁。这一过程诱导“肿瘤细胞死亡-表位扩增-随后肿瘤清除”的循环。这些数据表明，膳食共生可被识别并发展为“肿瘤生物素”，用于多层次的癌症治疗。
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