Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma.
Shlomi FinkinDetian YuanIlan SteinKoji TaniguchiAchim WeberKristian UngerJeffrey L BrowningNicolas GoossensShigeki NakagawaGanesh GunasekaranMyron E SchwartzMasahiro KobayashiHiromitsu KumadaMichael BergerOrit PappoKlaus RajewskyYujin HoshidaMichael KarinMathias HeikenwalderYinon Ben-NeriahEli PikarskyPublished in: Nature immunology (2015)
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.
Keyphrases
- poor prognosis
- cancer therapy
- long non coding rna
- mouse model
- transcription factor
- immune response
- high resolution
- papillary thyroid
- signaling pathway
- drug delivery
- oxidative stress
- squamous cell
- nuclear factor
- pi k akt
- inflammatory response
- cell proliferation
- mass spectrometry
- toll like receptor
- young adults
- liver injury
- genome wide identification