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Title:
Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma | Nature Immunology
Description:
Ectopic lymphoid structures develop at sites of chronic inflammation and are generally thought to be beneficial in the control of cancer. Pikarsky and colleagues show that these structures can instead nurture liver tumor progenitor cells. Ectopic lymphoid-like structures (ELSs) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicated poor prognosis for hepatocellular carcinoma (HCC). We studied an HCC mouse model that displayed abundant ELSs and found that they constituted immunopathological microniches wherein malignant hepatocyte progenitor cells appeared and thrived in a complex cellular and cytokine milieu until gaining self-sufficiency. The egress of progenitor cells and tumor formation were associated with the autocrine production of cytokines previously provided by the niche. ELSs developed via cooperation between the innate immune system and adaptive immune system, an event facilitated by activation of the transcription factor NF-κB and abolished by depletion of T cells. Such aberrant immunological foci might represent new targets for cancer therapy.
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accession number e-mtab-3848] nature portfolio permissions reprints privacy policy alb-cre-tnf−treated nuclear extract author information authors advertising nature 431 nature social media transcription factor nf-κb european research council lymphoid organ development den-treated alb-cre control yinon ben-neriah replaces baff-receptor signals japan society definite round-shaped clusters laser capture micro-dissection n-nitrosodiethylamine mechanistic data tumor necrosis factor tailed students t-test] tailed students t-test cancer research tnf-treated alb-cre tnf-treated alb-cre 30'/60' bulk multi-omics analysis springerlink instant access cell development functional b-cell response diethylnitrosamine-induced liver cancer canonical nf-κb activity early-stage colorectal cancers nf-κb dna binding permissions control alb-cre mice alb-cre control mice els gene signature intra-els hcc progenitors hep den-treated liver small-cell lung cancer de/dih/webviewer high power fields single-cell atlas nf-kappab functions myc-trp53−/− liver tumors ltβr-ig treated ikkβ autocrine il-6 signaling innate immune system t-cell infiltration
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- 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?
- Lymphotoxin's link to carcinogenesis: friend or foe?
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headline:Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma
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description:Ectopic lymphoid structures develop at sites of chronic inflammation and are generally thought to be beneficial in the control of cancer. Pikarsky and colleagues show that these structures can instead nurture liver tumor progenitor cells. Ectopic lymphoid-like structures (ELSs) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicated poor prognosis for hepatocellular carcinoma (HCC). We studied an HCC mouse model that displayed abundant ELSs and found that they constituted immunopathological microniches wherein malignant hepatocyte progenitor cells appeared and thrived in a complex cellular and cytokine milieu until gaining self-sufficiency. The egress of progenitor cells and tumor formation were associated with the autocrine production of cytokines previously provided by the niche. ELSs developed via cooperation between the innate immune system and adaptive immune system, an event facilitated by activation of the transcription factor NF-κB and abolished by depletion of T cells. Such aberrant immunological foci might represent new targets for cancer therapy.
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