Prdm1 Positively Regulates Liver Group 1 ILCs Cancer Immune Surveillance and Preserves Functional Heterogeneity

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 ofPrdm1in shaping the composition and maturation of cNK cells. AlthoughPrdm1did not affect the killing function of cNK cells in anin vivocytotoxicity model, a significant increase in cancer metastasis was observed inPrdm1knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly inPrdm1deficient cNK cells and liver ILC1s. scRNA sequencing 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.