美国斯隆-凯特林研究所Joan Massagué、Dana Pe’er等研究人员合作发现，肺癌转移中存在再生谱系和免疫介导的削减。这一研究成果2020年2月10日在线发表在国际学术期刊《自然—医学》上。

研究人员发现，人类原发性肺腺癌的特征是再生细胞类型的出现（通常在肺损伤反应中可见），以及在大多数肺泡和支气管上皮谱系分化相关的转录因子中出现大量混乱。相比之下，转移灶富集了关键的内胚层和肺特异性转录因子SOX2和SOX9，并涵盖了干细胞样到再生性肺上皮祖细胞状态大量原始转录程序。这种发育连续性反映了小鼠模型中转移性休眠自发爆发的进展阶段，并表现出对自然杀伤细胞的SOX9依赖性抗性。自然杀伤细胞耗竭引发了大量转移灶中发育阶段特异性限制的丧失，这提示了转移过程中发育可塑性与免疫介导的削减之间存在动态互作。

据了解，正常组织再生相关的发育过程与癌症有关，但在肿瘤进展过程中以及在免疫监视的选择压力下其发挥程度仍然未知。

附：英文原文

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