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Proc. Natl. Acad. Sci. USA, April 23, 2018, 201715295 | https://doi.org/10.1073/pnas.1715295115
Complex role of NK cells in regulation of oncolytic virus–bortezomib therapy
Yangjin Kima,b,1, Ji Young Yooc,1, Tae Jin Leec, Joseph Liud, Jianhua Yue, Michael A. Caligiurif, Balveen Kaurc,2, and Avner Friedmana,g,2
aMathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210; bDepartment of Mathematics, Konkuk University, Seoul, 143-701, Republic of Korea; cDepartment of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX 77030; dDepartment of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210; eDivision of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210; fDivision of Administration, City of Hope National Medical Center, Duarte, CA 91010; and gDepartment of Mathematics, The Ohio State University, Columbus, OH 43210
1Y.K. and J.Y.Y. contributed equally to this work.
aMathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210; bDepartment of Mathematics, Konkuk University, Seoul, 143-701, Republic of Korea; cDepartment of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX 77030; dDepartment of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210; eDivision of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210; fDivision of Administration, City of Hope National Medical Center, Duarte, CA 91010; and gDepartment of Mathematics, The Ohio State University, Columbus, OH 43210
1Y.K. and J.Y.Y. contributed equally to this work.
2To whom correspondence may be addressed.
Abstract
In the present work, we investigated the role of natural killer (NK) cells in combination therapy with oncolytic virus (OV) and bortezomib, a proteasome inhibitor. NK cells display rapid and potent immunity to metastatic and hematological cancers, and they overcome immunosuppressive effects of tumor microenvironment. We developed a mathematical model to address the question of how the density of NK cells affects the growth of the tumor. We found that the antitumor efficacy increases when the endogenous NKs are depleted and also when exogenous NK cells are injected into the tumor. These predictions were validated by our in vivo and in vitro experiments.
oncolytic virus | NK cells | bortezomib | partial differential equations models | tumor microenvironment
oncolytic virus | NK cells | bortezomib | partial differential equations models | tumor microenvironment
논문정보
- Research article
- 2018년 04월 (BRIC 등록일 2018-05-03)
- 국내+국외 연구진
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