韩国浦项工业大学Sin-Hyeog Im和韩国生物开放创新中心Dipayan Rudra课题组合作取得一项新成果。他们发现一种膳食共生微生物，通过激活肿瘤巨噬细胞铁固存来增强抗肿瘤免疫。2024年4月25日出版的《自然-免疫学》杂志发表了这项成果。

研究人员发现食物共生菌植物乳杆菌（Lactiplantibacillus plantarum IMB19），能增强同系小鼠和异种移植肿瘤模型小鼠的抗肿瘤免疫。植物乳杆菌的胶囊杂多糖是主要的效应分子，其是TLR2的配体。它通过双管齐下的方式，使肿瘤相关巨噬细胞偏向经典的活跃表型，从而产生持续的CD8⁺ T细胞反应，并触发巨噬细胞的"营养免疫"，其利用高亲和性铁转运体脂褐素-2在肿瘤微环境中捕获和封存铁。

这一过程会诱导肿瘤细胞死亡、表位扩展以及肿瘤清除循环过程。这些数据共同表明，食物共生物可能被识别并开发为"肿瘤生物"，从而实现多层次癌症治疗。

据了解，先天免疫细胞可产生多种抗肿瘤免疫反应，包括保护铁等必需营养物质。这些细胞可受共生细菌的调节；然而，识别和理解这种调节机制具有一定挑战性。

附：英文原文

Title: A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron

Author: Sharma, Garima, Sharma, Amit, Kim, Inhae, Cha, Dong Gon, Kim, Somi, Park, Eun Seo, Noh, Jae Gyun, Lee, Juhee, Ku, Ja Hyeon, Choi, Yoon Ha, Kong, JungHo, Lee, Haena, Ko, Haeun, Lee, Juhun, Notaro, Anna, Hong, Seol Hee, Rhee, Joon Haeng, Kim, Sang Geon, De Castro, Cristina, Molinaro, Antonio, Shin, Kunyoo, Kim, Sanguk, Kim, Jong Kyoung, Rudra, Dipayan, Im, Sin-Hyeog

Issue&Volume: 2024-04-25

Abstract: 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 Lactiplantibacillusplantarum 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.

DOI: 10.1038/s41590-024-01816-x

Source: https://www.nature.com/articles/s41590-024-01816-x