방사선생물학

본문글자크기
  • [Nat Immunol] CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation

    Icahn School of Medicine at Mount Sinai / Miriam Merad*

  • 출처
    Nat Immunol
  • 등재일
    2015 Oct
  • 저널이슈번호
    16(10):1060-8. doi: 10.1038/ni.3270. Epub 2015 Sep 7.
  • 내용

    바로가기  >

    Abstract

    Treatment with ionizing radiation (IR) can lead to the accumulation of tumor-infiltrating regulatory T cells (Treg cells) and subsequent resistance of tumors to radiotherapy. Here we focused on the contribution of the epidermal mononuclear phagocytes Langerhans cells (LCs) to this phenomenon because of their ability to resist depletion by high-dose IR. We found that LCs resisted apoptosis and rapidly repaired DNA damage after exposure to IR. In particular, we found that the cyclin-dependent kinase inhibitor CDKN1A (p21) was overexpressed in LCs and that Cdkn1a(-/-) LCs underwent apoptosis and accumulated DNA damage following IR treatment. Wild-type LCs upregulated major histocompatibility complex class II molecules, migrated to the draining lymph nodes and induced an increase in Treg cell numbers upon exposure to IR, but Cdkn1a(-/-) LCs did not. Our findings suggest a means for manipulating the resistance of LCs to IR to enhance the response of cutaneous tumors to radiotherapy.

    Comment in
    Subversion of anticancer immunosurveillance by radiotherapy. [Nat Immunol. 2015]

     

    Author information

    Price JG1,2, Idoyaga J1,2,3, Salmon H1,2, Hogstad B1,2, Bigarella CL4, Ghaffari S1,4,5,6, Leboeuf M1,2, Merad M1,2.
    1 Department of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    2 Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    3 Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, USA.
    4 Department of Developmental &Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    5 Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    6 Department of Medicine, Division of Hematology, Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 

     

  • 편집위원

    방사선치료시 발생하는 tumor-infiltrating regulatory T cells (Treg cells)의 축적과 이로 인한 방사선저항성의 획득에 관한 분자적 기전을 설명한 논문입니다. 이 과정에서 epidermal mononuclear phagocytes Langerhans cells (LCs)이 cyclin-dependent kinase inhibitor CDKN1A (p21)의 과발현을 통해 IR에 의한 세포사멸을 회피함으로써 방사선저항성을 유도함을 밝혔으며, 이를 통해 방사선저항성 극복을 위한 새로운 전략을 수립할 수 있음을 규명한 논문입니다

    2016-01-05 15:55:29

  • 덧글달기
    덧글달기
       IP : 44.197.195.36

    등록