Granulocytes Acquire Antiapoptosis Activity and Promote Tumor Growth during Tumor Progress.

Han Li,Wenyan Shen,Zien Wang,Yanjie Xu,Zequn Ding,Zhiyuan Xie,Linghao Wang,Yan Zhang

doi:10.1055/s-0041-1726335

Abstract

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.

Highlights

For a long time, the cognition of granulocyte function was limited to nonspecific immunity of sterilization and proinflammatory
The Percentage of Apoptotic Granulocytes Decreased during Tumor Progression First, we used AKR esophagus cancer mouse model to examine the percentage of apoptosis cells in total myeloid cells during tumor progression
Granulocytes and monocytes were separated by Ly6g and Ly6c in CD11bþ myeloid cells by FCM (►Fig. 1A), and their apoptosis was examined by annexin V and PI

Summary

Introduction

The cognition of granulocyte function was limited to nonspecific immunity of sterilization and proinflammatory. Studies have shown that they cannot only inhibit tumor occurrence and development and show the opposite effect. Mature granulocytes will undergo spontaneous apoptosis in a short time to maintain the total number of granulocytes in the body. The apoptosis of granulocytes is of great significance for maintaining the homeostasis of the organism and eliminating inflammation.[3,4] Under certain inflammatory conditions, the apoptosis of granulocytes is accelerated, the proportion increases, and the life course of the cells changes.[5,6] there are not many studies on the apoptosis of granulocytes in tumors, and the function of granulocytes with altered apoptosis is unclear

Methods

Results

Conclusion