@article{f8390fe82c8e4b44aa4c4b8e4abb15a6,
title = "ISG15 promotes ERK1 ISGylation, CD8+ T cell activation and suppresses ovarian cancer progression",
abstract = "Increased number of tumor-infiltrating CD8+ lymphocytes is associated with improved survival in patients with advanced stage high grade serous ovarian cancer (HGSOC) but the underlying molecular mechanism has not been thoroughly explored. Using transcriptome profiling of microdissected HGSOC tissue with high and low CD8+ lymphocyte count and subsequent validation studies, we demonstrated that significantly increased ISG15 (Interferon-stimulated gene 15) expression in HGSOC was associated with high CD8+ lymphocyte count and with the improvement in median overall survival in both univariate and multivariate analyses. Further functional studies showed that endogenous and exogenous ISG15 suppressed ovarian cancer progression through ISGylation of ERK in HGSOC, and activation of NK cells and CD8+ T lymphocytes. These data suggest that the development of treatment strategies based on up-regulating ISG15 in ovarian cancer cells or increased circulating ISG15 in ovarian cancer patients is warranted.",
keywords = "CD8+ lymphocyte, ISG15, ISGylation, Interferon, Ovarian cancer",
author = "Yeung, {Tsz Lun} and Tsai, {Ching Chou} and Leung, {Cecilia S.} and Yeung, {Chi Lam Au} and Thompson, {Melissa S.} and Lu, {Karen H.} and Freedman, {Ralph S.} and Birrer, {Michael J.} and Wong, {Kwong Kwok} and Mok, {Samuel C.}",
note = "Funding Information: Funding: This study was supported in part by grants R01CA169200 (M.J.B., S.C.M.), R01CA142832 (M.J.B.), the University of Texas MD Anderson Cancer Center Ovarian Cancer Specialized Program of Research Excellence grant P50CA083639 (S.C.M., K.-K.W.), the University of Texas MD Anderson Cancer Center Endometrial Cancer Specialized Program of Research Excellence grant P50CA098258 (S.C.M.) and MD Anderson Support Grant P30CA016672 from the National Institutes of Health; the U.S. Department of Health and Human Services; grant W81XWH-17-1-0126 (S.C.M) from the Ovarian Cancer Research Program, Department of Defense; grant POE/MDACC/02.2011 (T.-L.Y.) from the Ovarian Cancer Research Fund and grant CMRPG8C0841 (C.C.T.) from the Chang Gung Memorial Hospital, Kaohsiung, Taiwan. Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2018",
month = dec,
doi = "10.3390/cancers10120464",
language = "English (US)",
volume = "10",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "12",
}