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Proc Natl Acad Sci U S A. 2018 May 8;115(19):4927-4932. doi: 10.1073/pnas.1715295115. Epub 2018 Apr 23.

Complex role of NK cells in regulation of oncolytic virus-bortezomib therapy.

Author information

1
Mathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210.
2
Department of Mathematics, Konkuk University, Seoul, 143-701, Republic of Korea.
3
Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX 77030.
4
Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210.
5
Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
6
Division of Administration, City of Hope National Medical Center, Duarte, CA 91010.
7
Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX 77030; afriedman@math.osu.edu Balveen.Kaur@uth.tmc.edu.
8
Mathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210; afriedman@math.osu.edu Balveen.Kaur@uth.tmc.edu.
9
Department of Mathematics, The Ohio State University, Columbus, OH 43210.

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.

KEYWORDS:

NK cells; bortezomib; oncolytic virus; partial differential equations models; tumor microenvironment

PMID:
29686060
PMCID:
PMC5948955
DOI:
10.1073/pnas.1715295115
[Indexed for MEDLINE]
Free PMC Article

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