CD300ld on neutrophils is required for tumour-driven immune suppression
中性粒细胞上的 CD300ld 是肿瘤驱动的免疫抑制所必需的。
Chaoxiong Wang, Xichen Zheng, Jinlan Zhang, Xiaoyi Jiang, Jia Wang, Yuwei Li, Xiaonan Li, Guanghui Shen, Jiayin Peng, Peixuan Zheng, Yunqing Gu, Jiaojiao Chen, Moubin Lin, Changwen Deng, Hai Gao, Zhigang Lu, Yun Zhao, Min Luo (2023) CD300ld on neutrophils is required for tumour-driven immune suppression Nature (IF: 48.5) 1 区 621(7980) 830-839Abstract
The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy1,2. Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance2-4. Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Links
http://www.ncbi.nlm.nih.gov/pubmed/37674079http://dx.doi.org/10.1038/s41586-023-06511-9
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