Regenerative lineages and immune-mediated pruning in lung cancer metastasis
Ashley M. Laughney,Jing Hu,Nathaniel R. Campbell,Nathaniel R. Campbell,Samuel F. Bakhoum,Manu Setty,Vincent-Philippe Lavallée,Yubin Xie,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 Pe'er,Joan Massagué +20 more
TLDR
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.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. Single-cell analysis of lung cancer progression uncovers developmental and regenerative programs co-opted by cancer cells and immune-mediated pruning during metastatic outbreakread more
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The updated landscape of tumor microenvironment and drug repurposing.
Ming-Zhu Jin,Weilin Jin +1 more
TL;DR: An updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism micro environment, acidic niche, innervated niche, and mechanical microenvironment is presented and conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin are summarized in new antitumor application.
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Targeting metastatic cancer.
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The cancer–natural killer cell immunity cycle
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The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future.
Maria C. Basil,Jeremy Katzen,Anna Engler,Minzhe Guo,Michael J. Herriges,Jaymin J. Kathiriya,Rebecca Windmueller,Alexandra B. Ysasi,William J. Zacharias,H.A. Chapman,Darrell N. Kotton,Jason R. Rock,Hans-Willem Snoeck,Gordana Vunjak-Novakovic,Jeffrey A. Whitsett,Edward E. Morrisey +15 more
TL;DR: Key aspects of lung repair and regeneration are discussed, including the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung Repair and regeneration.
Journal ArticleDOI
Emergence of a High-Plasticity Cell State during Lung Cancer Evolution
Nemanja D. Marjanovic,Nemanja D. Marjanovic,Matan Hofree,Jason E. Chan,David Canner,Katherine Wu,Marianna Trakala,Griffin Hartmann,Olivia Smith,Olivia Smith,Jonathan Y. Kim,Jonathan Y. Kim,Kelly V. Evans,Anna Hudson,Orr Ashenberg,Caroline B. M. Porter,Alborz Bejnood,Ayshwarya Subramanian,Kenneth L. Pitter,Yan Yan,Toni Delorey,Devan Phillips,Nisargbhai S. Shah,Ojasvi Chaudhary,Alexander M. Tsankov,Alexander M. Tsankov,Travis J. Hollmann,Natasha Rekhtman,Pierre P. Massion,John T. Poirier,Linas Mazutis,Ruifang Li,Joo-Hyeon Lee,Angelika Amon,Charles M. Rudin,Tyler Jacks,Aviv Regev,Tuomas Tammela,Tuomas Tammela +38 more
TL;DR: This study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS, which is associated with poor survival across human cancers and demonstrates chemoresistance in mice.
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