Department of Anatomy, University of California, San Francisco, CA 94143-0452;
Department of Clinical Sciences, Division of Clinical Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21704-21714. doi: 10.1073/pnas.1907660116. Epub 2019 Oct 7.
Metastatic behavior varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between nonmetastatic primary breast cancer and innate immune response, acting together to control metastatic progression. The primary tumor systemically recruits IFNγ-producing immune effector monocytes to the lung. IFNγ up-regulates in neutrophils and enhances their killing capacity. The immune effector monocytes and tumoricidal neutrophils target disseminated tumor cells in the lungs, preventing metastatic outgrowth. Importantly, our findings could underlie the development of immunotherapeutic target molecules that augment the function of immune effector monocytes and neutrophils.
转移性乳腺癌的行为差异很大。解释为什么大多数乳腺癌患者从未发生转移性生长的机制在很大程度上是缺失的，但可能是新的免疫治疗靶分子发展的基础。在这里，我们展示了非转移性原发性乳腺癌与先天免疫反应之间的相互作用，共同控制转移性进展。原发性肿瘤系统募集 IFNγ 产生的免疫效应单核细胞到肺部。IFNγ 上调中性粒细胞中的基因表达，并增强其杀伤能力。免疫效应单核细胞和杀瘤中性粒细胞靶向肺部的播散性肿瘤细胞，防止转移性生长。重要的是，我们的发现可以为增强免疫效应单核细胞和中性粒细胞功能的免疫治疗靶分子的发展提供基础。
