Li Han, Shen Wenyan, Xu Yanjie, Wang Zien, Wang Linghao, Ding Zequn, Xie Zhiyuan, Zhang Yan
Med-X Research Institute & School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Department of Clinical Laboratory, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Glob Med Genet. 2021 Jun;8(2):72-77. doi: 10.1055/s-0041-1726335. Epub 2021 Mar 16.
Granulocytes play important roles in cancer, and their apoptotic status is often changed by the influence of tumor environment. However, the changes and the function on granulocyte apoptosis in cancer are unclear. In this study, we used tumor-bearing mouse model and tumor patients to analyzed the apoptosis of granulocytes in different tissues by flow analysis and TUNEL fluorescence staining, and found that the percentage of apoptosis cells in granulocytes was significantly decreased in late-stage tumor-bearing mouse and patients. The in vitro co-culture experiment showed that these antiapoptotic granulocytes could significantly inhibit T cell proliferation, and RNA-seq proved that there was obvious difference on the transcriptome between these cells and control cells, particularly immune-related genes. What is important, adoptive transfer of these antiapoptotic granulocytes promoted tumor progress in mouse model. Conclusively, we found that granulocytes in late-stage tumor could delay the process of apoptosis, inhibit T cell proliferation, and acquire pro-tumor activity, which provides a new therapeutic target for tumor immunity.
粒细胞在癌症中发挥着重要作用，其凋亡状态常受肿瘤环境影响而改变。然而，癌症中粒细胞凋亡的变化及其功能尚不清楚。在本研究中，我们利用荷瘤小鼠模型和肿瘤患者，通过流式分析和TUNEL荧光染色分析不同组织中粒细胞的凋亡情况，发现荷瘤晚期小鼠和患者中粒细胞凋亡细胞的百分比显著降低。体外共培养实验表明，这些抗凋亡粒细胞可显著抑制T细胞增殖，RNA测序证明这些细胞与对照细胞在转录组上存在明显差异，尤其是免疫相关基因。重要的是，在小鼠模型中过继转移这些抗凋亡粒细胞可促进肿瘤进展。总之，我们发现晚期肿瘤中的粒细胞可延缓凋亡进程，抑制T细胞增殖，并获得促肿瘤活性，这为肿瘤免疫提供了一个新的治疗靶点。
