文章：

NK细胞介导静脉注射卡介苗对小鼠肺转移的预防作用

NK cells mediate preventive efficacy of intravenous BCG against lung metastasis in mice 

原文发布日期：2025-08-02 

英文摘要：

Lung metastases frequently arise from primary tumors, including bladder cancer, and represent a critical negative prognostic factor. Natural Killer (NK) cells have shown to play a vital role in controlling metastasis. Consequently, tumor cells have evolved specific mechanisms to evade NK cell-mediated immune surveillance, promoting metastasis and resistance to immunotherapy. In this study, we investigated the prophylactic and therapeutic potential of intravenous Bacillus Calmette–Guerin (BCG) in preventing lung metastases from bladder cancer cells using a murine model. We demonstrated that prophylactic BCG administration significantly reduced tumor burden and prolonged survival, largely through NK cell activation. However, BCG treatment was ineffective when administered over established tumors, likely due to tumor-driven immune evasion mechanisms. Our results revealed the contribution of interferon-gamma (IFN-γ) to tumor resistance. Tumor cells exposed to IFN-γ were more resistant to BCG in vivo, which correlated with the overexpression of immune checkpoint molecules, whereas disruption of the IFN-γ signaling pathway in tumor cells partially restored the therapeutic efficacy of BCG. Our findings highlight the importance of understanding tumor immune escape mechanisms and suggest that BCG could be a promising treatment for preventing lung metastases in bladder cancer. 

摘要翻译：

肺转移常源于膀胱癌等原发性肿瘤，是重要的不良预后因素。自然杀伤（NK）细胞已被证实在控制转移中起关键作用。因此，肿瘤细胞进化出特定机制来逃避NK细胞介导的免疫监视，从而促进转移并导致免疫治疗耐药。本研究通过小鼠模型探讨了静脉注射卡介苗（BCG）预防膀胱癌细胞肺转移的预防与治疗潜力。我们发现预防性BCG给药能显著降低肿瘤负荷并延长生存期，该作用主要通过NK细胞活化实现。然而，BCG对已形成的肿瘤治疗无效，可能与肿瘤驱动的免疫逃逸机制有关。研究结果揭示了干扰素-γ（IFN-γ）对肿瘤耐药性的贡献：暴露于IFN-γ的肿瘤细胞在体内对BCG更具耐药性，且这种特性与免疫检查点分子的过表达相关；而阻断肿瘤细胞中的IFN-γ信号通路可部分恢复BCG的治疗效果。我们的研究结果强调了理解肿瘤免疫逃逸机制的重要性，并表明BCG可能成为预防膀胱癌肺转移的有效疗法。

原文链接：

NK cells mediate preventive efficacy of intravenous BCG against lung metastasis in mice