Antitumor Immunity Produced by the Liver Kupffer Cells, NK Cells, NKT Cells, and CD8⁺CD122⁺T Cells

Abstract

Mouse and human livers contain innate immune leukocytes, NK cells, NKT cells, and macrophage-lineage Kupffer cells. Various bacterial components, including Toll-like receptor (TLR) ligands and an NKT cell ligand (α-galactocylceramide), activate liver Kupffer cells, which produce IL-1, IL-6, IL-12, and TNF. IL-12 activates hepatic NK cells and NKT cells to produce IFN-γ, which further activates hepatic T cells, in turn activating phagocytosis and cytokine production by Kupffer cells in a positive feedback loop. These immunological events are essentially evoked to protect the host from bacterial and viral infections; however, these events also contribute to antitumor and antimetastatic immunity in the liver by activated liver NK cells and NKT cells. Bystander CD8+CD122+ T cells, and tumor-specific memory CD8+T cells, are also induced in the liver by α-galactocylceramide. Furthermore, adoptive transfer experiments have revealed that activated liver lymphocytes may migrate to other organs to inhibit tumor growth, such as the lungs and kidneys. The immunological mechanism underlying the development of hepatocellular carcinoma in cirrhotic livers in hepatitis C patients and liver innate immunity as a double-edged sword (hepatocyte injury/regeneration, septic shock, autoimmune disease, etc.) are also discussed.

Effect of Balanites aegyptiaca on Ehrlich Ascitic carcinoma growth and metastasis in Swiss mice

“…The reported activated Kuppfer cell enforced the potential hepatic anti-metastatic activity of balanite extract through apoptosis. Seki et al (2011) observed the concurrence of apoptosis in tumor cells in concomitant with appearance of activated Kuppfer cells. He clarified that Kuppfer cells produced cytotoxic factors; NO, TNF and IFN.…”

Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing

“…One possible explanation for this discrepancy might be ascribed to the complex immunologic system of the liver. For example, among the innate immune components containing dozens of leukocytes and antigen-presenting cells [21, 22], Kuppffer cells, which reside as stationary macrophages in the liver sinusoids, have been shown to perform functions of trapping, phagocytosing, and elimination [23] even for targets of circulating tumor cells and circulating DNAs [24, 25]. If the concentration of mutation fragments of ctDNA was far less than that of DNA derived from tissues without mutations, our evaluation of plasma DNA might miss such mutations [20].…”

Tim-3 pathway affects NK cell impairment in patients with active tuberculosis

“…Previous studies have revealed that NK cells essentially produce IFN-c under IL-12 and LPS stimulation [35]. Therefore, the IFN-c secretion and degranulation potential of NK cells from active TB patients was determined by stimulation with IL-12 and LPS in vitro.…”