文章：

乳酸乳球菌乳脂亚种C60通过改变代谢偏好增强抗肿瘤免疫力并上调巨噬细胞功能

Lactococcus lactissubsp.cremorisC60 Upregulates Macrophage Function by Modifying Metabolic Preference in Enhanced Anti-Tumor Immunity

原文发布日期：18 May 2024

DOI: 10.3390/cancers16101928

类型: Article

开放获取: 是

英文摘要：

Lactococcus lactissubsp.cremorisC60 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.

摘要翻译： 

乳酸乳球菌乳脂亚种C60是一种乳酸菌益生菌株，可在髓系细胞中诱导多种免疫修饰。这些修饰随后调控T细胞功能，从而增强局部和全身免疫。本研究报道，在小鼠黑色素瘤模型中，C60通过代谢重编程增强巨噬细胞功能，进而增加三磷酸腺苷（ATP）生成，从而抑制肿瘤生长。与生理盐水组相比，C60灌胃给药显著降低了小鼠的肿瘤体积。C60给药组小鼠肿瘤内巨噬细胞的抗肿瘤功能显著上调，表现为炎症表型（M1）增强而非抗炎/修复表型（M2），同时抗原提呈能力提升，导致肿瘤抗原特异性CD8+ T细胞增多。通过功能分析，我们发现C60使肿瘤内巨噬细胞建立以糖酵解为主导的代谢模式（而非脂肪酸氧化），从而提升细胞内ATP水平。针对口服C60为何能在远端部位发挥作用的问题，我们发现细菌细胞壁成分可能从肠道分布至全身，通过激活Toll样受体信号通路在外周巨噬细胞中诱导刺激信号。因此，C60通过TLR介导的刺激促进巨噬细胞代谢向糖酵解主导转变，从而增强能量产出，最终强化巨噬细胞的抗肿瘤免疫。

原文链接：

Lactococcus lactissubsp.cremorisC60 Upregulates Macrophage Function by Modifying Metabolic Preference in Enhanced Anti-Tumor Immunity