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  • [Nat Commun.] PD-L1 is an activation-independent marker of brown adipocytes.

    Massachusetts Institute of Technology / Hidde L. Ploegh*

  • 출처
    Nat Commun.
  • 등재일
    2017 Sep 21
  • 저널이슈번호
    8(1):647. doi: 10.1038/s41467-017-00799-8.
  • 내용

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    Abstract

    Programmed death ligand 1 (PD-L1) is expressed on a number of immune and cancer cells, where it can downregulate antitumor immune responses. Its expression has been linked to metabolic changes in these cells. Here we develop a radiolabeled camelid single-domain antibody (anti-PD-L1 VHH) to track PD-L1 expression by immuno-positron emission tomography (PET). PET-CT imaging shows a robust and specific PD-L1 signal in brown adipose tissue (BAT). We confirm expression of PD-L1 on brown adipocytes and demonstrate that signal intensity does not change in response to cold exposure or β-adrenergic activation. This is the first robust method of visualizing murine brown fat independent of its activation state.Current approaches to visualise brown adipose tissue (BAT) rely primarily on markers that reflect its metabolic activity. Here, the authors show that PD-L1 is expressed on brown adipocytes, does not change upon BAT activation, and that BAT volume in mice can be measured by PET-CT with a radiolabeled anti-PD-L1 antibody. 

     

    Author information

    Ingram JR1,2, Dougan M1,3, Rashidian M1, Knoll M1, Keliher EJ4,5, Garrett S6, Garforth S6, Blomberg OS1, Espinosa C1, Bhan A7, Almo SC6, Weissleder R4,5,8, Lodish H1,9, Dougan SK2,10, Ploegh HL11,12.

    Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.

    Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.

    Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, 02114, USA.

    Center for Systems Biology, Massachusetts General Hospital, Boston, MA, 02114, USA.

    Department of Radiology, Massachusetts General Hospital, Boston, MA, 02114, USA.

    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.

    Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.

    Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.

    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.

    10 Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, 02115, USA.

    11 Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA. Hidde.Ploegh@childrens.harvard.edu.

    12 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA. Hidde.Ploegh@childrens.harvard.edu. 

  • 편집위원

    cancer immunotherapy에서 중요한 marker로 대두되는 PD-L1을 imaging할 수 있는 PET agent를 in vivo로 실험하면서 brown adipocytes의 activation을 반영한다는 사실도 함께 보여준 paper입니다.

    2017-10-17 17:31:19

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