美国加州大学Devon A. Lawson研究组揭示了小胶质细胞促进抗肿瘤免疫，抑制乳腺癌脑转移(BCBM)。相关论文发表在2023年11月13日出版的《自然—细胞生物学》杂志上。

通过单细胞RNA测序、遗传和人源化小鼠模型，他们特异性地鉴定了小胶质细胞，并发现它们在BCBM中发挥了明显的促炎和肿瘤抑制作用。缺乏小胶质细胞的动物表现出转移增加、存活率降低、自然杀伤细胞和T细胞反应降低，表明小胶质细胞在促进抗肿瘤免疫以抑制BCBM方面至关重要。他们发现，促炎反应在人类小胶质细胞中是保守的，其反应的标志物与BCBM患者更好的预后相关。这些发现确立了小胶质细胞在抗肿瘤免疫中的重要作用，并突出了它们作为脑转移的潜在免疫治疗靶点。

据介绍，BCBM是一种致命疾病，目前尚无有效的治疗方法。先前的研究表明，脑癌和转移瘤中密集浸润着抗炎、产蛋白的肿瘤相关巨噬细胞，但脑内小胶质细胞的作用仍然存在争议，因为很难将它们与其他肿瘤相关巨噬细胞区分开来。

附：英文原文

Title: Microglia promote anti-tumour immunity and suppress breast cancer brain metastasis

Author: Evans, Katrina T., Blake, Kerrigan, Longworth, Aaron, Coburn, Morgan A., Insua-Rodrguez, Jacob, McMullen, Timothy P., Nguyen, Quy H., Ma, Dennis, Lev, Tatyana, Hernandez, Grace A., Oganyan, Armani K., Orujyan, Davit, Edwards, Robert A., Pridans, Clare, Green, Kim N., Villalta, S. Armando, Blurton-Jones, Mathew, Lawson, Devon A.

Issue&Volume: 2023-11-13

Abstract: Breast cancer brain metastasis (BCBM) is a lethal disease with no effective treatments. Prior work has shown that brain cancers and metastases are densely infiltrated with anti-inflammatory, protumourigenic tumour-associated macrophages, but the role of brain-resident microglia remains controversial because they are challenging to discriminate from other tumour-associated macrophages. Using single-cell RNA sequencing, genetic and humanized mouse models, we specifically identify microglia and find that they play a distinct pro-inflammatory and tumour-suppressive role in BCBM. Animals lacking microglia show increased metastasis, decreased survival and reduced natural killer and T cell responses, showing that microglia are critical to promote anti-tumour immunity to suppress BCBM. We find that the pro-inflammatory response is conserved in human microglia, and markers of their response are associated with better prognosis in patients with BCBM. These findings establish an important role for microglia in anti-tumour immunity and highlight them as a potential immunotherapy target for brain metastasis.

DOI: 10.1038/s41556-023-01273-y

Source: https://www.nature.com/articles/s41556-023-01273-y