Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, China; Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Le Gao
Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, China
Peiying Wang
Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, China
Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, United States
Yiran Zheng
Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, China
Yumo Zhang
Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, China
Jiaman Sun
Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, China
Xue Li
Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, China
Jiming Wang
Tianjin Economic-Technological Development Area (TEDA) Hospital, Tianjin, China
Xiao-Hong Li
Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, China
Huaiyong Chen
Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, China; College of Pulmonary and Critical Care Medicine, 8th Medical Center, Chinese PLA General Hospital, Beijing, China; Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin, China
Zhouxin Yang
Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Zhejiang Hospital, Hangzhou, China
Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1-deficient cNK cells and liver ILC1s. Single-cell RNA sequencing (scRNA-seq) data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s, and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.
