Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets
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DOI：
10.1016/j.ccell.2019.02.009
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发表时间：
2019-04-15
期刊：
影响因子：
50.3
通讯作者：
Pollard, Jeffrey W.
中科院分区：
文献类型：
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作者：
Cassetta, Luca;Fragkogianni, Stamatina;Pollard, Jeffrey W.
肿瘤相关巨噬细胞(TAMs)和循环单核细胞在人类癌症中的作用知之甚少。在这里，我们表明单核细胞亚群分布和转录本显著改变子宫内膜癌和乳腺癌的存在。此外，来自子宫内膜癌和乳腺癌的TAM在转录上不同于单核细胞及其各自的组织驻留巨噬细胞。我们确定了乳腺的特征，该特征在侵袭性乳腺癌亚型中高度丰富，并与较短的疾病特异性生存期有关。我们还发现了TAMs和癌细胞之间的自动调节环，由肿瘤坏死因子α驱动，涉及SIGLEC1和CCL8，这是通过产生CSF1自我增强的。总而言之，这些数据提供了直接证据，表明单核细胞和巨噬细胞转录情况受到癌症的干扰，反映了患者的预后。
The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.