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.

先天免疫细胞产生多方面的抗肿瘤免疫反应，包括保存铁等必需营养素。这些细胞可以被共生细菌调节；然而，识别和理解这是如何发生的是一个挑战。在这里，我们展示了食品共生植物乳杆菌 IMB19增强了同基因和异种移植小鼠肿瘤模型的抗肿瘤免疫力。其荚膜杂多糖是主要效应分子，作为 TLR2 的配体。它以双管齐下的方式使肿瘤相关巨噬细胞偏向经典活性表型，从而产生持续的 CD8 ⁺ T 细胞反应，并触发巨噬细胞“营养免疫”以部署高亲和力铁转运蛋白 lipocalin-2在肿瘤微环境中捕获和隔离铁。这个过程诱导肿瘤细胞死亡、表位扩张和随后的肿瘤清除的循环。这些数据共同表明，食物共生体可能会被识别并开发成“致癌素”，用于癌症治疗的多层方法。