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Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer.
Shiao, Stephen L; Gouin, Kenneth H; Ing, Nathan; Ho, Alice; Basho, Reva; Shah, Aagam; Mebane, Richard H; Zitser, David; Martinez, Andrew; Mevises, Natalie-Ya; Ben-Cheikh, Bassem; Henson, Regina; Mita, Monica; McAndrew, Philomena; Karlan, Scott; Giuliano, Armando; Chung, Alice; Amersi, Farin; Dang, Catherine; Richardson, Heather; Shon, Wonwoo; Dadmanesh, Farnaz; Burnison, Michele; Mirhadi, Amin; Zumsteg, Zachary S; Choi, Rachel; Davis, Madison; Lee, Joseph; Rollins, Dustin; Martin, Cynthia; Khameneh, Negin H; McArthur, Heather; Knott, Simon R V.
  • Shiao SL; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: stephen.shiao@cshs.org.
  • Gouin KH; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ing N; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ho A; Breast Cancer Clinical Research Unit, Duke University Medical Center, Raleigh, NC, USA. Electronic address: alice.ho@duke.edu.
  • Basho R; Ellison Institute of Technology, Los Angeles, CA, USA.
  • Shah A; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Mebane RH; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Zitser D; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Martinez A; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Mevises NY; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ben-Cheikh B; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Henson R; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Mita M; Department of Medicine, Division of Hematology-Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • McAndrew P; Department of Medicine, Division of Hematology-Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Karlan S; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Giuliano A; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Chung A; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Amersi F; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Dang C; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Richardson H; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Shon W; Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Dadmanesh F; Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Burnison M; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Mirhadi A; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Zumsteg ZS; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Choi R; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Davis M; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Lee J; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Rollins D; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Martin C; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Khameneh NH; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • McArthur H; Department of Internal Medicine, Division of Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: heather.mcarthur@utsouthwestern.edu.
  • Knott SRV; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: simon.knott@cshs.org.
Cancer Cell ; 42(1): 70-84.e8, 2024 01 08.
Article en En | MEDLINE | ID: mdl-38194915
ABSTRACT
Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article