乳酸乳球菌亚种。 cremoris C60 是一种乳酸菌 (LAB) 益生菌菌株，可诱导骨髓谱系细胞发生多种免疫修饰。这些修饰随后调节 T 细胞功能，从而增强局部和全身的免疫力。在此，我们报告 C60 通过代谢改变增强巨噬细胞功能来抑制肿瘤生长，从而增加小鼠黑色素瘤模型中三磷酸腺苷 (ATP) 的产生。与小鼠体内施用盐水相比，胃内（例如）施用 C60 显着减小了肿瘤体积。在给予 C60 的小鼠中，肿瘤内 (IT) 巨噬细胞的抗肿瘤功能上调，炎症表型 (M1) 增加而不是抗炎/修复 (M2) 表型增加，同时抗原呈递能力增强，导致肿瘤抗原特异性 CD8 T 细胞增加。通过这种功能修饰，我们发现 C60 在 IT 巨噬细胞中建立了以糖酵解为主的代谢，而不是脂肪酸氧化 (FAO)，从而导致细胞内 ATP 水平增加。为了解决为什么口服补充 C60 在远端发挥功能的问题，我们发现细菌细胞壁成分（可从肠道分布到全身）可能通过 Toll 样受体（TLR）在外周巨噬细胞中诱导刺激信号。 ) 信号激活。因此，C60 通过在 TLR 介导的刺激下促进主要代谢转向糖酵解来增强巨噬细胞抗肿瘤免疫，从而增加大量能量产生。

Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently regulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic alterations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was upregulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced antigen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.