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dc.contributor.authorRegev, Aviv
dc.date.accessioned2022-09-19T18:59:27Z
dc.date.available2021-10-27T20:30:53Z
dc.date.available2022-09-19T18:59:27Z
dc.date.issued2021
dc.identifier.urihttps://hdl.handle.net/1721.1/136118.2
dc.description.abstractImmune checkpoint blockade (ICB) results in durable disease control in a subset of patients with advanced renal cell carcinoma (RCC), but mechanisms driving resistance are poorly understood. We characterize the single-cell transcriptomes of cancer and immune cells from metastatic RCC patients before or after ICB exposure. In responders, subsets of cytotoxic T cells express higher levels of co-inhibitory receptors and effector molecules. Macrophages from treated biopsies shift toward pro-inflammatory states in response to an interferon-rich microenvironment but also upregulate immunosuppressive markers. In cancer cells, we identify bifurcation into two subpopulations differing in angiogenic signaling and upregulation of immunosuppressive programs after ICB. Expression signatures for cancer cell subpopulations and immune evasion are associated with PBRM1 mutation and survival in primary and ICB-treated advanced RCC. Our findings demonstrate that ICB remodels the RCC microenvironment and modifies the interplay between cancer and immune cell populations critical for understanding response and resistance to ICB.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1016/j.ccell.2021.02.015en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceElsevieren_US
dc.titleTumor and immune reprogramming during immunotherapy in advanced renal cell carcinomaen_US
dc.typeArticleen_US
dc.contributor.departmentHoward Hughes Medical Instituteen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.relation.journalCancer Cellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2021-07-23T16:36:50Z
dspace.orderedauthorsBi, K; He, MX; Bakouny, Z; Kanodia, A; Napolitano, S; Wu, J; Grimaldi, G; Braun, DA; Cuoco, MS; Mayorga, A; DelloStritto, L; Bouchard, G; Steinharter, J; Tewari, AK; Vokes, NI; Shannon, E; Sun, M; Park, J; Chang, SL; McGregor, BA; Haq, R; Denize, T; Signoretti, S; Guerriero, JL; Vigneau, S; Rozenblatt-Rosen, O; Rotem, A; Regev, A; Choueiri, TK; Van Allen, EMen_US
dspace.date.submission2021-07-23T16:36:52Z
mit.journal.volume39en_US
mit.journal.issue5en_US
mit.licensePUBLISHER_CC
mit.metadata.statusPublication Information Neededen_US


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