(1/n) Delighted to share our work using #scRNAseq to explore the intersection between regeneration, development and #immune recognition in #cancer #metastasis online @NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague
nature.com/articles/s4159…
nature.com/articles/s4159…
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (2/n) human primary #lungcancer is characterized by the emergence of regenerative cell types, typically seen in response to lung injury, but showing striking lineage promiscuity (identity confused!)
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (3/n) #metastasis exhibits a continuum of more primitive stem to epithelial progenitor states – driven in large part by key embryonic and lung-specifying transcription factors, SOX2 and SOX9.
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (4/n) Surprisingly, expression of #inflammatory pathways was highly variable across developmental states observed in metastases, which engendered distinct susceptibilities to innate #immune cell killing.
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (5/n) For instance, metastasis-initiating cells, enriched for the core stem cell transcription factor SOX2, were more sensitive to NK cells when evoking regenerative programs.
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (6/n) Conversely, more differentiated lung progenitors, specified by SOX9, displayed increased resistance to NK cell-mediated killing in a spontaneous model of metastatic escape in vivo and upon co-culture with activated NK cells in vitro.
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (7/n) Depletion of NK cells facilitated the emergence of diverse #cancer cell subpopulations during #metastasis, including the outgrowth of phenotypic states otherwise suppressed.
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (8/n) Therefore, there is a dynamic interplay between the #immune system and developmental pathways in #cancer #metastasis leading to developmental stage-specific immune vulnerabilities. We hope that this work will shed light on ways to tackle #metastasis initiating #stemcells!
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (9/n) If you are interested in working at the intersection between #cancer #metastasis, the #immune system, using #scRNAseq, we are seeking talented #postdocs and students @WeillCornell; please RT and apply at laughneylab.com
@NatureMedicine @sloan_kettering @WeillCornell @scell_papers @dana_peer @LabMassague (10/n) Thanks to our many collaborators! @dana_peer @LabMassague @charlesrudin @natasharekhtman @SettyM @Samuel_Bakhoum
