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Bone morphogenetic protein 7 promotes resistance to immunotherapy

Author

Listed:
  • Maria Angelica Cortez

    (The University of Texas MD Anderson Cancer Center)

  • Fatemeh Masrorpour

    (The University of Texas MD Anderson Cancer Center)

  • Cristina Ivan

    (The University of Texas MD Anderson Cancer Center)

  • Jie Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Ahmed I. Younes

    (The University of Texas MD Anderson Cancer Center)

  • Yue Lu

    (The University of Texas MD Anderson Cancer Center)

  • Marcos R Estecio

    (The University of Texas MD Anderson Cancer Center)

  • Hampartsoum B. Barsoumian

    (The University of Texas MD Anderson Cancer Center)

  • Hari Menon

    (The University of Texas MD Anderson Cancer Center)

  • Mauricio da Silva Caetano

    (The University of Texas MD Anderson Cancer Center)

  • Rishab Ramapriyan

    (The University of Texas MD Anderson Cancer Center)

  • Jonathan E. Schoenhals

    (The University of Texas MD Anderson Cancer Center)

  • Xiaohong Wang

    (The University of Texas MD Anderson Cancer Center)

  • Ferdinandos Skoulidis

    (The University of Texas MD Anderson Cancer Center)

  • Mark D. Wasley

    (The University of Texas MD Anderson Cancer Center)

  • George Calin

    (The University of Texas MD Anderson Cancer Center)

  • Patrick Hwu

    (The University of Texas MD Anderson Cancer Center)

  • James W. Welsh

    (The University of Texas MD Anderson Cancer Center)

Abstract

Immunotherapies revolutionized cancer treatment by harnessing the immune system to target cancer cells. However, most patients are resistant to immunotherapies and the mechanisms underlying this resistant is still poorly understood. Here, we report that overexpression of BMP7, a member of the TGFB superfamily, represents a mechanism for resistance to anti-PD1 therapy in preclinical models and in patients with disease progression while on immunotherapies. BMP7 secreted by tumor cells acts on macrophages and CD4+ T cells in the tumor microenvironment, inhibiting MAPK14 expression and impairing pro-inflammatory responses. Knockdown of BMP7 or its neutralization via follistatin in combination with anti-PD1 re-sensitizes resistant tumors to immunotherapies. Thus, we identify the BMP7 signaling pathway as a potential immunotherapeutic target in cancer.

Suggested Citation

  • Maria Angelica Cortez & Fatemeh Masrorpour & Cristina Ivan & Jie Zhang & Ahmed I. Younes & Yue Lu & Marcos R Estecio & Hampartsoum B. Barsoumian & Hari Menon & Mauricio da Silva Caetano & Rishab Ramap, 2020. "Bone morphogenetic protein 7 promotes resistance to immunotherapy," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18617-z
    DOI: 10.1038/s41467-020-18617-z
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