Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients co-transplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy.

中文翻译：

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人G-MDSC是处于不同成熟阶段的嗜中性粒细胞，可促进乳腺癌中肿瘤的生长。

已知髓样抑制细胞（MDSC）有助于癌症的免疫逃逸。但是，人类粒细胞（G）-MDSC子集在肿瘤进展过程中的功能很大程度上是未知的，并且在人类肿瘤标本中没有可用于鉴定它们的确定标记。使用基因表达谱，流式细胞仪和肿瘤微阵列，我们在这里证明了人类G-MDSCs以嗜中性粒细胞的形式出现在不同的成熟阶段，并具有疾病特异性的特征。源自转移性乳腺癌和恶性黑色素瘤患者的G-MDSC显示出独特的未成熟中性粒细胞谱，与健康的供体中性粒细胞相比，与败血症患者的G-MDSC更相似。最后，我们表明，与乳腺癌细胞共移植的转移性乳腺癌患者的原发性G-MDSC促进了肿瘤的生长，并影响血管形成，导致髓样免疫细胞被排斥。我们的发现揭示了人类G-MDSC在肿瘤进展中的作用，并且对靶向免疫治疗也有临床意义。