The unique role of innate lymphoid cells in cancer and the hepatic microenvironment

Abstract

Cancer is a complex disease, and despite incredible progress over the last decade, it remains the leading cause of death worldwide. Liver cancers, including hepatocellular carcinoma (HCC), and liver metastases are distinct from other cancers in that they typically emerge as a consequence of long-term low-grade inflammation. Understanding the mechanisms that underpin inflammation-driven tissue remodeling of the hepatic immune environment is likely to provide new insights into much needed treatments for this devastating disease. Group 1 innate lymphoid cells (ILCs), which include natural killer (NK) cells and ILC1s, are particularly enriched in the liver and thought to contribute to the pathogenesis of a number of liver diseases, including cancer. NK cells are an attractive, but underexplored, therapeutic target in hepatic disease due to their role in immunosurveillance and their ability to recognize and eliminate malignant cells. ILC1s are closely related to and share many phenotypic features with NK cells but are less well studied. Thus, their utility in immunotherapeutic approaches is not yet well understood. Here, we review our current understanding of ILCs in cancer with a particular focus on liver and liver-related diseases.

NK cell marker gene-based model shows good predictive ability in prognosis and response to immunotherapies in hepatocellular carcinoma

“…Investigating the internal mechanisms that underlie inflammation-driven tissue remodeling of the hepatic immune environment might help to provide novel approaches into much needed treatments for this devastating disease. Immune cells in the liver play crucial roles in the initiation and progression of HCC 4 . NK cells, a group of adaptive immune cells, are abundantly enriched in the liver and thought to contribute to the pathogenesis of liver cancer 21 .…”

“…NK cells, a group of adaptive immune cells, are abundantly enriched in the liver and thought to contribute to the pathogenesis of liver cancer 21 . Hence, they are potential therapeutic targets, albeit underexplored given their important role in immunosurveillance and their capability to recognize and eliminate tumor cells 4 .…”

“…A growing number of studies have focused on the regulation of immune cell-mediated functions in the tumor microenvironment (TME) of HCC 3 . The TME in HCC has prominent roles in tumor initiation and progression, and the relevant immune features have been defined 4 , 5 . Several literatures support that genomic signatures have strong correlations with response to immune checkpoint inhibitors, which might provide evidence of available biomarkers to guide clinical decision-making 3 .…”

“…Natural killer (NK) cells have been reported as important members of the innate immune system, which are involved in direct tumor cell killing in response to immunotherapies 6 . They are an attractive therapeutic target in liver disease due to their role in immunosurveillance and their ability to recognize and eliminate malignant cells 4 . NK cells are also particularly enriched in the liver and have been recognized to contribute to the pathogenesis of liver cancer 7 .…”

Function of Innate Lymphoid Cells in Periodontal Tissue Homeostasis: A Narrative Review

“…CILPs can differentiate into at least two different precursors: NK progenitors (NKPs), which can give rise to cNK cells; and common helper ILC progenitors (CHILPs), which can differentiate into all ILC subpopulations [ 38 ]. CHILPs express Id2 and CD127 and contain two groups: the group of cells that express PLZF (promyelocytic leukemia zinc finger), called ILC precursor cells (ILCps), and a population of RORγt+ PLZF− cells, which highly express TOX and not GATA3, called lymphoid tissue inducer precursors (LTips) [ 39 ]. LTips differentiate into LTi cells, and ILCps can further differentiate into ILC1s, ILC2s, and ILC3s, depending on the transcription factors T-bet, GATA-3, and RORγt [ 40 ].…”