美研究發(fā)現(xiàn)：肺癌轉移中存在再生譜系和免疫介導的削減
美國斯隆-凱特林研究所Joan Massagué、Dana Pe’er等研究人員合作發(fā)現(xiàn)，肺癌轉移中存在再生譜系和免疫介導的削減。這一研究成果2020年2月10日在線發(fā)表在國際學術期刊《自然—醫(yī)學》上。
研究人員發(fā)現(xiàn)，人類原發(fā)性肺腺癌的特征是再生細胞類型的出現(xiàn)（通常在肺損傷反應中可見），以及在大多數(shù)肺泡和支氣管上皮譜系分化相關的轉錄因子中出現(xiàn)大量混亂。相比之下，轉移灶富集了關鍵的內(nèi)胚層和肺特異性轉錄因子SOX2和SOX9，并涵蓋了干細胞樣到再生性肺上皮祖細胞狀態(tài)大量原始轉錄程序。這種發(fā)育連續(xù)性反映了小鼠模型中轉移性休眠自發(fā)爆發(fā)的進展階段，并表現(xiàn)出對自然殺傷細胞的SOX9依賴性抗性。自然殺傷細胞耗竭引發(fā)了大量轉移灶中發(fā)育階段特異性限制的喪失，這提示了轉移過程中發(fā)育可塑性與免疫介導的削減之間存在動態(tài)互作。
據(jù)了解，正常組織再生相關的發(fā)育過程與癌癥有關，但在腫瘤進展過程中以及在免疫監(jiān)視的選擇壓力下其發(fā)揮程度仍然未知。
附：英文原文
Title: Regenerative lineages and immune-mediated pruning in lung cancer metastasis
Author: Ashley M. Laughney, Jing Hu, Nathaniel R. Campbell, Samuel F. Bakhoum, Manu Setty, Vincent-Philippe Lavalle, Yubin Xie, Ignas Masilionis, Ambrose J. Carr, Sanjay Kottapalli, Viola Allaj, Marissa Mattar, Natasha Rekhtman, Joao B. Xavier, Linas Mazutis, John T. Poirier, Charles M. Rudin, Dana Peer, Joan Massagu
Issue&Volume: 2020-02-10
Abstract: Developmental processes underlying normal tissue regeneration have been implicated in cancer, but the degree of their enactment during tumor progression and under the selective pressures of immune surveillance, remain unknown. Here we show that human primary lung adenocarcinomas are characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. In contrast, metastases are enriched for key endoderm and lung-specifying transcription factors, SOX2 and SOX9, and recapitulate more primitive transcriptional programs spanning stem-like to regenerative pulmonary epithelial progenitor states. This developmental continuum mirrors the progressive stages of spontaneous outbreak from metastatic dormancy in a mouse model and exhibits SOX9-dependent resistance to natural killer cells. Loss of developmental stage-specific constraint in macrometastases triggered by natural killer cell depletion suggests a dynamic interplay between developmental plasticity and immune-mediated pruning during metastasis.
DOI: 10.1038/s41591-019-0750-6
Source: https://www.nature.com/articles/s41591-019-0750-6
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