RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Therapeutic exploration of combined local hyperthermia and anti-CD200 blockade therapy in the EMT6 breast cancer model.
Therapeutic exploration of combined local hyperthermia and anti-CD200 blockade therapy in the EMT6 breast cancer model.
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乳腺癌仍是全球女性癌症相关死亡的主要原因。联合治疗常被用于提高治疗效果并降低复发风险。热疗(HT)作为一种微创治疗,已显示出增强免疫治疗效果的潜力。在EMT6乳腺肿瘤模型中,CD200表达升高与肿瘤进展相关,且已有报道阻断CD200/CD200R信号通路可增强抗肿瘤免疫应答。本研究在临床前小鼠模型中对局部HT联合抗CD200阻断的治疗效果进行了初步评估。通过皮下接种在Balb/c小鼠中建立EMT6肿瘤。接种后第7、8、9天施加局部HT,并在第7、9、11天腹腔注射抗CD200单克隆抗体。联合治疗显著减缓了肿瘤进展并提高了生存率。此外,治疗小鼠引流淋巴结中CD8+ T细胞活化增加,肿瘤内T细胞和自然杀伤(NK)细胞浸润增强,同时免疫抑制性调节性T细胞(Tregs)和髓源性抑制细胞(MDSCs)显著减少。这些发现凸显了需要进一步研究以验证并更好地理解该联合方案在乳腺癌中的治疗潜力。
Breast cancer remains the leading cause of cancer-related deaths among women worldwide. Combinatorial therapies are often employed to improve treatment efficacy and reduce the risk of recurrence. Hyperthermia (HT), a minimally invasive treatment, has shown potential to enhance immunotherapy outcomes. In the EMT6 breast tumor model, elevated CD200 expression is associated with tumor progression, and blockade of the CD200/CD200R signaling pathway has been reported to enhance anti-tumor immune responses.
This study presents a preliminary evaluation of the therapeutic effects of local HT combined with anti-CD200 blockade in a preclinical mouse model. EMT6 tumors were established in Balb/c mice via subcutaneous inoculation. Local HT was applied on days 7, 8, and 9 post-inoculation, and anti-CD200 monoclonal antibody was administered intraperitoneally on days 7, 9, and 11. The combination therapy significantly reduced tumour progression and improved survival.
Moreover, treated mice showed increased activation of CD8 + T cells in draining lymph nodes and enhanced tumor infiltration by T cells and natural killer (NK) cells, alongside a marked reduction in immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs).
These findings highlight the need for further studies to validate and better understand the therapeutic potential of this combination approach in breast cancer.
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