Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma.
Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma.
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DOI：
10.1038/ni.3290
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发表时间：
2015-12
影响因子：
30.5
通讯作者：
Pikarsky E
中科院分区：
文献类型：
--
作者：
Finkin S;Yuan D;Stein I;Taniguchi K;Weber A;Unger K;Browning JL;Goossens N;Nakagawa S;Gunasekaran G;Schwartz ME;Kobayashi M;Kumada H;Berger M;Pappo O;Rajewsky K;Hoshida Y;Karin M;Heikenwalder M;Ben-Neriah Y;Pikarsky E
异位淋巴样结构（ELS）经常在癌症中观察到，但其功能尚不清楚。虽然 ELS 表明某些恶性肿瘤的预后良好，但我们发现肝脏 ELS 表明肝细胞癌 (HCC) 的预后较差。我们研究了 HCC 小鼠模型，显示出丰富的 ELS，发现它们构成了免疫病理学微生态位，其中恶性肝细胞祖细胞出现并在复杂的细胞和细胞因子环境中茁壮成长，直到获得自给自足。祖细胞排出和肿瘤形成与先前由生态位提供的细胞因子的自分泌产生相关。 ELS 是在先天性免疫系统和适应性免疫系统之间合作的基础上发展起来的，这种合作由 NF-κB 激活促进，并通过 T 细胞耗竭而消除。这些异常的免疫灶可能成为癌症治疗的新靶点。
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.