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Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma.
Bi, Kevin; He, Meng Xiao; Bakouny, Ziad; Kanodia, Abhay; Napolitano, Sara; Wu, Jingyi; Grimaldi, Grace; Braun, David A; Cuoco, Michael S; Mayorga, Angie; DelloStritto, Laura; Bouchard, Gabrielle; Steinharter, John; Tewari, Alok K; Vokes, Natalie I; Shannon, Erin; Sun, Maxine; Park, Jihye; Chang, Steven L; McGregor, Bradley A; Haq, Rizwan; Denize, Thomas; Signoretti, Sabina; Guerriero, Jennifer L; Vigneau, Sébastien; Rozenblatt-Rosen, Orit; Rotem, Asaf; Regev, Aviv; Choueiri, Toni K; Van Allen, Eliezer M.
Afiliação
  • Bi K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • He MX; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Boston, MA 02115, USA.
  • Bakouny Z; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Kanodia A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Napolitano S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Wu J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Grimaldi G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Braun DA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Cuoco MS; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Mayorga A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • DelloStritto L; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Bouchard G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Steinharter J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Tewari AK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Vokes NI; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Shannon E; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Sun M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Park J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Chang SL; Division of Urology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • McGregor BA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Haq R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Denize T; Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Signoretti S; Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Guerriero JL; Harvard Medical School, Boston, MA 02115, USA; Breast Tumor Immunology Laboratory, Women's Cancer Program, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Vigneau S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Rozenblatt-Rosen O; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Rotem A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Regev A; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Choueiri TK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Van Allen EM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: eliezerm_vanallen@dfci.harvard.edu.
Cancer Cell ; 39(5): 649-661.e5, 2021 05 10.
Article em En | MEDLINE | ID: mdl-33711272
ABSTRACT
Immune 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Microambiente Tumoral / Fatores Imunológicos / Imunoterapia / Neoplasias Renais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Microambiente Tumoral / Fatores Imunológicos / Imunoterapia / Neoplasias Renais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article