Roy Konkonika, Kozłowski Henryk Mikołaj, Jędrzejewski Tomasz, Sobocińska Justyna, Maciejewski Bartosz, Dzialuk Artur, Wrotek Sylwia
Department of Immunology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 1 Lwowska Street, 87-100 Torun, Poland.
Department of Genetics, Faculty of Biological Sciences, Kazimierz Wielki University, 10 Powstańców Wielkopolskich Ave., 85-090 Bydgoszcz, Poland.
Cancers (Basel). 2023 Oct 23;15(20):5113. doi: 10.3390/cancers15205113.
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 (Mo) 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. Mo-derived factors increased cancer cell viability, motility, and clonogenicity, suggesting a conducive environment for cancer development. Remarkably, despite reduced TNFα and IL-6 levels, Mo exhibited 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，可保护宿主免受因身体反复接触脂多糖（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，在此过程中可观察到巨噬细胞发生显著的重编程，我们推测它可能通过改变肿瘤环境来影响癌症发展。本研究旨在探讨ET是否通过改变肿瘤微环境来影响癌症进展。通过直接相互作用和条件培养基暴露，研究了内毒素耐受巨噬细胞（Mo）对乳腺癌和结肠癌细胞的影响。我们通过活力、克隆形成潜力、运动性、划痕试验和三维球体试验来表征癌细胞行为。Mo衍生因子增加了癌细胞的活力、运动性和克隆形成能力，表明为癌症发展营造了有利环境。值得注意的是，尽管肿瘤坏死因子α（TNFα）和白细胞介素-6（IL-6）水平降低，但Mo仍表现出M1极化。这些发现揭示了一种与ET相关的巨噬细胞重编程，为各种肿瘤的癌症进展营造了有利环境。针对ET可能成为癌症治疗和预防的一个有前景的途径。
