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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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- 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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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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