Regenerative lineages and immune-mediated pruning in lung cancer metastasis Journal Article


Authors: Laughney, A. M.; Hu, J.; Campbell, N. R.; Bakhoum, S. F.; Setty, M.; Lavallée, V. P.; Xie, Y.; Masilionis, I.; Carr, A. J.; Kottapalli, S.; Allaj, V.; Mattar, M.; Rekhtman, N.; Xavier, J. B.; Mazutis, L.; Poirier, J. T.; Rudin, C. M.; Pe’er, D.; Massagué, J.
Article Title: Regenerative lineages and immune-mediated pruning in lung cancer metastasis
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. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Journal Title: Nature Medicine
Volume: 26
Issue: 2
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2020-02-01
Start Page: 259
End Page: 269
Language: English
DOI: 10.1038/s41591-019-0750-6
PUBMED: 32042191
PROVIDER: scopus
PMCID: PMC7021003
DOI/URL:
Notes: Article -- Export Date: 2 March 2020 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Natasha Rekhtman
    278 Rekhtman
  2. Joan Massague
    360 Massague
  3. Joao Debivar Xavier
    67 Xavier
  4. Manu Setty
    24 Setty
  5. Charles Rudin
    231 Rudin
  6. Samuel F Bakhoum
    22 Bakhoum
  7. Viola   Allaj
    7 Allaj
  8. Jing   Hu
    6 Hu
  9. Marissa   Mattar
    19 Mattar
  10. Dana Pe'er
    39 Pe'er
  11. Ambrose James Carr
    3 Carr
  12. Linas Mazutis
    14 Mazutis
  13. Yubin Xie
    2 Xie