Endotoxin tolerance (ET) is an adaptive phenomenon of the immune system that protects the host from clinical complications due to repeated exposure of the body to endotoxins such as lipopolysaccharide (LPS). Since ET is an immunosuppressive mechanism in which a significant reprogramming of macrophages is observed, we hypothesized that it could influence cancer development by modifying the tumour environment. This study aimed to explore whether ET influences cancer progression by altering the tumour microenvironment. Endotoxin-tolerant macrophages (MoET) were examined for their impact on breast and colon cancer cells via direct interaction and conditioned media exposure. We characterized cancer cell behaviour by viability, clonogenic potential, motility, scratch assays, and 3D spheroidal assays. MoET-derived factors increased cancer cell viability, motility, and clonogenicity, suggesting a conducive environment for cancer development. Remarkably, despite reduced TNFα and IL-6 levels, MoETexhibited M1 polarization. These findings uncover an ET-associated macrophage reprogramming that fosters a favourable context for cancer progression across diverse tumours. Targeting ET could emerge as a promising avenue for cancer therapy and prevention.
内毒素耐受（ET）是免疫系统的一种适应性现象，能够保护宿主因反复暴露于脂多糖（LPS）等内毒素而引发的临床并发症。由于ET是一种免疫抑制机制，其中可观察到巨噬细胞的显著重编程，我们推测其可能通过改变肿瘤环境影响癌症发展。本研究旨在探讨ET是否通过改变肿瘤微环境影响癌症进展。通过直接相互作用和条件培养基暴露，我们检测了内毒素耐受巨噬细胞（MoET）对乳腺癌和结肠癌细胞的影响。我们通过细胞活力、克隆形成能力、运动能力、划痕实验及3D球体实验来表征癌细胞行为。MoET来源的因子增强了癌细胞的活力、运动能力和克隆形成能力，表明其营造了有利于癌症发展的微环境。值得注意的是，尽管TNFα和IL-6水平降低，MoET仍表现出M1极化特征。这些发现揭示了ET相关的巨噬细胞重编程机制，该机制为多种肿瘤的进展创造了有利条件。靶向ET可能成为癌症治疗和预防的新策略。
Endotoxin Tolerance Creates Favourable Conditions for Cancer Development
肿瘤(癌症)患者之家