@article{aa2c89896f2046d89303e893d04409f2,
title = "Increased vessel perfusion predicts the efficacy of immune checkpoint blockade",
abstract = "Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV-PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy. Moreover, globally enhanced tumor vessel perfusion could be detected by Doppler ultrasonography before changes in tumor size, which predicted final therapeutic efficacy with more than 90% sensitivity and specificity. Mechanistically, CD8+ T cell depletion, IFN-γ neutralization, or implantation of tumors in IFN-γ receptor knockout mice abrogated the vessel perfusion enhancement and antitumor effects of ICB. These results demonstrated that ICB increased vessel perfusion by promoting CD8+ T cell accumulation and IFN-γ production, indicating that increased vessel perfusion reflects the successful activation of antitumor T cell immunity by ICB. Our findings suggest that vessel perfusion can be used as a novel noninvasive indicator for predicting ICB responsiveness.",
author = "Xichen Zheng and Zhaoxu Fang and Xiaomei Liu and Shengming Deng and Pei Zhou and Xuexiang Wang and Chenglin Zhang and Rongping Yin and Haitian Hu and Xiaolan Chen and Yijie Han and Yun Zhao and Lin, {Steven H.} and Songbing Qin and Xiaohua Wang and Kim, {Betty Y.S.} and Penghui Zhou and Wen Jiang and Qingyu Wu and Yuhui Huang",
note = "Funding Information: We are grateful to Rakesh K. Jain (Harvard Medical School), Yufang Shi (Soochow University), Suling Liu (University of Science and Technology of China), Zhihai Qin (Institute of Biophysics, Chinese Academy of Sciences), Zhinan Yin (Jinan University), Yuting Ma (Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences), Xiaoren Zhang (Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences), and Youfa Duan (Sun Yat-Sen University Cancer Center) for technical support and expert advice. This work was supported in part by the National Natural Science Foundation of China grants 81673004 and 81372245 (to YH), the National Program on Key Research Project of China 2016YFC1302400 (to YH), the Distinguished Professors of Jiangsu Province fund SR21100114 (to YH), the Collaborative Innovation Center of Hematology, the Priority Academic Program Development of Jiangsu Higher Education Institutions, the National Institute of Neurological Disorders and Stroke grant R01 NS104315 (to BYSK), the American Society of Clinical Oncology Conquer Cancer Foundation Young Investigator Award (to WJ), and the National Cancer Institute{\textquoteright}s Cancer Center Support (Core) grant CA016672 (to the University of Texas MD Anderson Cancer Center). The authors also thank C. Wogan of the MD Anderson Cancer Center{\textquoteright}s Division of Radiation Oncology for editorial assistance. Publisher Copyright: {\textcopyright} 2018 Academic Press. All rights reserved.",
year = "2018",
month = may,
day = "1",
doi = "10.1172/JCI96582",
language = "English (US)",
volume = "128",
pages = "2104--2115",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",
}