Ectopic lymphoid-like structures (ELS) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicate poor prognosis in hepatocellular carcinoma (HCC). We studied an HCC mouse model, displaying abundant ELSs and found that they constitute immunopathological microniches, wherein progenitor malignant hepatocytes appear and thrive in a complex cellular and cytokine milieu until gaining self-sufficiency. Progenitor egression and tumor formation is associated with autocrine production of cytokines previously provided by the niche. ELSs develop upon cooperation between the innate and adaptive immune system which is facilitated by NF-κB activation and abolished by T cell depletion. These aberrant immune foci could be new targets for cancer therapy.

While both compounds are highly potent anti-inflammatory agents, AN1284 is more effective in mitigating the underlying causes of GalN/LPS-induced acute liver failure in mice.

The role of the NF-κB signaling pathway in liver cancer is complex. While some evidence suggests that in the liver, like in many other organ systems, NF-κB is oncogenic, there is strong evidence showing that in certain liver cancer models NF-κB suppresses tumorigenesis. These contrasting findings cannot be dismissed on technicalities and are likely due to the complex nature of the NF-κB response. Similar contrasting findings regarding NF-κB activity are revealed in skin cancer models. Thus, it is possible that the contradictory role of NF-κB in tumorigenesis is a general phenomenon and not an oddity related solely to the liver. Further studies are indicated to decipher the underlying molecular mechanisms. Revealing these mechanisms may facilitate the identification of patient subgroups and specific situations in which NF-κB inhibition will be a preferred therapeutic option. Moreover, it is possible that specific interventions could boost the tumor suppressor functions of NF-κB in tumors that harbor mutations that render this pathway constitutively active.