Bone morphogenetic protein 7 promotes resistance to immunotherapy

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 Ramapriyan, Jonathan E. Schoenhals, Xiaohong Wang, Ferdinandos Skoulidis, Mark D. Wasley, George Calin, Patrick Hwu and James W. Welsh
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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

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18617-z

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