A YAP/TAZ-CD54 axis is required for CXCR2 −CD44 − tumor-specific neutrophils to suppress gastric cancer

• DOI: 10.1093/procel/pwac045
• Publication Date: 2022-10-26T15:28:21Z
• Authors: Pingping Nie; Weihong Zhang; Yan Meng; Moubin Lin; Fenghua Guo; Hui Zhang; Zhenzhu Tong; Meng Wang; Fan Chen; Liwei An; Yang Tang; Yi Han; Ruixian Yu; Wenjia Wang; Yuanzhi Xu; Linxin Wei; Zhaocai Zhou; Shi Jiao
• Keywords: Tumor progression

Abstract As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44 −CXCR2 − as tumor-specific (tsNeus) both mouse and human gastric cancer (GC). We uncovered a Hippo regulon with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified epithelial and/or cells. Importantly, knockout YAP/TAZ neutrophiles impaired differentiation into CD54 + tsNeus reduced antitumor activity, leading accelerated GC progression. Moreover, the relative amounts were found be negatively associated progression positively patient survival. Interestingly, patients receiving neoadjuvant chemotherapy had increased numbers tsNeus. Furthermore, pharmacologically enhancing activity selectively activated suppress refractory GC, no significant inflammation-related side effects. Thus, our work characterized revealed essential role YAP/TAZ-CD54 axis tsNeus, opening new possibility develop neutrophil-based therapeutics.