Bone morphogenetic protein 7 promotes resistance to immunotherapy.

Autor: Cortez MA; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. MACortez@mdanderson.org., Masrorpour F; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ivan C; Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang J; Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Younes AI; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lu Y; Epigenetic and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Estecio MR; Epigenetic and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Barsoumian HB; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Menon H; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Caetano MDS; Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ramapriyan R; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Schoenhals JE; Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang X; Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Skoulidis F; Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wasley MD; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Calin G; Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hwu P; Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Welsh JW; Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Sep 24; Vol. 11 (1), pp. 4840. Date of Electronic Publication: 2020 Sep 24.
DOI: 10.1038/s41467-020-18617-z
Abstrakt: 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.
Databáze: MEDLINE