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Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

Journal

Publisher

MDPI
DOI: 10.3390/ijms22169044

Keywords

natural killer cells; innate lymphoid cells; ILC1; liver; hepatocellular carcinoma; cancer; immunotherapies

Funding

  1. CIHR
  2. CCS
  3. National Health and Medical Research Council (NHMRC) of Australia [GNT1098832, GNT1165443, GNT1135898, GNT2002265]
  4. Australian Research Career development Fellowship [GNT1123000]
  5. Cancer Council NSW [RG 21-05]
  6. Priority-driven Collaborative Cancer Research Scheme
  7. Cure Cancer [1158085]
  8. US Department of Defense-Breast Cancer Research Program-Breakthrough Award Level 1 [BC200025]
  9. UQ Diamantina Institute Laboratory Start-Up Package
  10. Cancer Australia

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NK cells and ILC1 are specific innate lymphoid cell subsets crucial for detecting and eliminating pathogens and cancer cells. In the liver, they contribute to organ homeostasis through cytokine production and elimination of harmful microbes, with potential for targeted immunotherapies in hepatocellular carcinoma. Understanding the distinct roles and functions of these innate immune cells in liver cancer could lead to new treatment strategies.
Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1) are specific innate lymphoid cell subsets that are key for the detection and elimination of pathogens and cancer cells. In liver, while they share a number of characteristics, they differ in many features. These include their developmental pathways, tissue distribution, phenotype and functions. NK cells and ILC1 contribute to organ homeostasis through the production of key cytokines and chemokines and the elimination of potential harmful bacteria and viruses. In addition, they are equipped with a wide range of receptors, allowing them to detect stressed cells' such as cancer cells. Our understanding of the role of innate lymphoid cells in hepatocellular carcinoma (HCC) is growing owing to the development of mouse models, the progress in immunotherapeutic treatment and the recent use of scRNA sequencing analyses. In this review, we summarize the current understanding of NK cells and ILC1 in hepatocellular carcinoma and discuss future strategies to take advantage of these innate immune cells in anti-tumor immunity. Immunotherapies hold great promise in HCC, and a better understanding of the role and function of NK cells and ILC1 in liver cancer could pave the way for new NK cell and/or ILC1-targeted treatment.

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