Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma

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.