DC Field | Value | Language |
---|---|---|
dc.contributor.author | Miao, Yuxuan | ko |
dc.contributor.author | Yang, Hanseul | ko |
dc.contributor.author | Levorse, John | ko |
dc.contributor.author | Yuan, Shaopeng | ko |
dc.contributor.author | Polak, Lisa | ko |
dc.contributor.author | Sribour, Megan | ko |
dc.contributor.author | Singh, Bhuvanesh | ko |
dc.contributor.author | Rosenblum, Michael D. | ko |
dc.contributor.author | Fuchs, Elaine | ko |
dc.date.accessioned | 2020-11-17T01:55:10Z | - |
dc.date.available | 2020-11-17T01:55:10Z | - |
dc.date.created | 2020-11-17 | - |
dc.date.created | 2020-11-17 | - |
dc.date.issued | 2019-05 | - |
dc.identifier.citation | CELL, v.177, no.5, pp.1172 - + | - |
dc.identifier.issn | 0092-8674 | - |
dc.identifier.uri | http://hdl.handle.net/10203/277320 | - |
dc.description.abstract | Our bodies are equipped with powerful immune surveillance to clear cancerous cells as they emerge. How tumor-initiating stem cells (tSCs) that form and propagate cancers equip themselves to overcome this barrier remains poorly understood. To tackle this problem, we designed a skin cancer model for squamous cell carcinoma (SCC) that can be effectively challenged by adoptive cytotoxic T cell transfer (ACT)-based immunotherapy. Using single-cell RNA sequencing (RNA-seq) and lineage tracing, we found that transforming growth factor beta (TGF-beta)-responding tSCs are superior at resisting ACT and form the root of tumor relapse. Probing mechanism, we discovered that during malignancy, tSCs selectively acquire CD80, a surface ligand previously identified on immune cells. Moreover, upon engaging cytotoxic T lymphocyte antigen-4 (CTLA4), CD80-expressing tSCs directly dampen cytotoxic T cell activity. Conversely, upon CTLA4- or TGF-beta-blocking immunotherapies or Cd80 ablation, tSCs become vulnerable, diminishing tumor relapse after ACT treatment. Our findings place tSCs at the crux of how immune checkpoint pathways are activated. | - |
dc.language | English | - |
dc.publisher | CELL PRESS | - |
dc.title | Adaptive Immune Resistance Emerges from Tumor-Initiating Stem Cells | - |
dc.type | Article | - |
dc.identifier.wosid | 000468103800011 | - |
dc.identifier.scopusid | 2-s2.0-85065542376 | - |
dc.type.rims | ART | - |
dc.citation.volume | 177 | - |
dc.citation.issue | 5 | - |
dc.citation.beginningpage | 1172 | - |
dc.citation.endingpage | + | - |
dc.citation.publicationname | CELL | - |
dc.identifier.doi | 10.1016/j.cell.2019.03.025 | - |
dc.contributor.localauthor | Yang, Hanseul | - |
dc.contributor.nonIdAuthor | Miao, Yuxuan | - |
dc.contributor.nonIdAuthor | Levorse, John | - |
dc.contributor.nonIdAuthor | Yuan, Shaopeng | - |
dc.contributor.nonIdAuthor | Polak, Lisa | - |
dc.contributor.nonIdAuthor | Sribour, Megan | - |
dc.contributor.nonIdAuthor | Singh, Bhuvanesh | - |
dc.contributor.nonIdAuthor | Rosenblum, Michael D. | - |
dc.contributor.nonIdAuthor | Fuchs, Elaine | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | PROPAGATING CELLS | - |
dc.subject.keywordPlus | IMMUNOTHERAPY | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | RNAI | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | SUPPRESSOR | - |
dc.subject.keywordPlus | EXPRESSION | - |
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