@article{5fb6fd25995f4bc4b129fda3075b0cd2,
title = "Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells",
abstract = "Although the efficacy of cancer radiotherapy (RT) can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified. Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer (BC) cells and RT-treated mouse syngeneic BC. Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis. CD47 is upregulated preferentially in HER2-expressing cells, and blocking CD47 or HER2 reduces both receptors with diminished clonogenicity and augmented phagocytosis. CRISPR-mediated CD47 and HER2 dual knockouts not only inhibit clonogenicity but also enhance macrophage-mediated attack. Dual antibody of both receptors synergizes with RT in control of syngeneic mouse breast tumor. These results provide the evidence that aggressive behavior of radioresistant BC is caused by CD47-mediated anti-phagocytosis conjugated with HER2-prompted proliferation. Dual blockade of CD47 and HER2 is suggested to eliminate resistant cancer cells in BC radiotherapy.",
author = "Demet Candas-Green and Bowen Xie and Jie Huang and Ming Fan and Aijun Wang and Cheikh Menaa and Yanhong Zhang and Lu Zhang and Di Jing and Soheila Azghadi and Weibing Zhou and Lin Liu and Nian Jiang and Tao Li and Tianyi Gao and Colleen Sweeney and Rulong Shen and Lin, {Tzu yin} and Pan, {Chong xian} and Ozpiskin, {Omer M.} and Gayle Woloschak and Grdina, {David J.} and Vaughan, {Andrew T.} and Wang, {Ji Ming} and Shuli Xia and Monjazeb, {Arta M.} and Murphy, {William J.} and Sun, {Lun Quan} and Chen, {Hong Wu} and Lam, {Kit S.} and Weichselbaum, {Ralph R.} and Li, {Jian Jian}",
note = "Funding Information: We thank Dr. Irmgard Feldman for sharing human breast cancer specimens. We acknowledge Dr. William Frazier for kindly providing anti-mouse CD47 MIAP301 hybridoma, Dr. Qian Chen for the assistance of in vivo macrophage phagocytosis, and Mr. Shuaib Juma and Dr. Julian Perks for conduction of radiation with in vivo mouse breast tumor model. This work was supported by NIH RO1 CA213830 (J.J.L.) and CA224900 (H.-W.C.), University of California Davis Cancer Center Cancer Immunology Pilot Grant Support, and University of California Davis NCI-designated Comprehensive Cancer Center supported by the CCSG Grant awarded by the National Cancer Institute (NIH NCI P30CA093373). Funding Information: Human breast cancer tissues. Fresh frozen HER2 positive and negative breast cancer tissues were provided by the UC Davis Comprehensive Cancer Center Biorepository (IRB # 283665, and IRB # 218204) funded by the UC Davis Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (NCI P30CA093373) with all patient information blocked except the diagnostic results. Additional human breast cancer pathological samples including the unstained 4-µm-thick sections of formalin-fixed paraffin-embedded (FFPE) paired primary breast cancer and recurrent breast cancers were obtained from the department of pathology, Ohio State University with research IRB approval (#2002H0089). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-18245-7",
language = "English (US)",
volume = "11",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
