Number of the records: 1

Tumor growth accelerated by chemotherapy-induced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines

SYSNO ASEP	0473062
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Tumor growth accelerated by chemotherapy-induced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines
Author(s)	Šímová, Jana (UMG-J)_RID Sapega, Olena (UMG-J) Imrichová, Terezie (UMG-J) Štěpánek, Ivan (UMG-J)_RID Kyjacová, Lenka (UMG-J) Mikyšková, Romana (UMG-J)_RID Indrová, Marie (UMG-J)_RID Bieblová, Jana (UMG-J) Bubeník, Jan (UMG-J) Bártek, Jiří (UMG-J)_RID Hodný, Zdeněk (UMG-J)_RID Reiniš, Milan (UMG-J)_RID
Number of authors	12
Source Title	OncoTarget. - : Impact Journals LLC - ISSN 1949-2553 Roč. 7, č. 34 (2016), s. 54952-54964
Number of pages	13
Language	eng - English
Country	US - United States
Keywords	cellular senescence ; cancer chemotherapy ; docetaxel ; IL-12 ; cell therapy
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	NT14461 GA MZd - Ministry of Health (MZ)
Institutional support	UMG-J - RVO:68378050
UT WOS	000385435000069
DOI	10.18632/oncotarget.10712
Annotation	Standard-of-care chemo-or radio-therapy can induce, besides tumor cell death, also tumor cell senescence. While senescence is considered to be a principal barrier against tumorigenesis, senescent cells can survive in the organism for protracted periods of time and they can promote tumor development. Based on this emerging concept, we hypothesized that elimination of such potentially cancer-promoting senescent cells could offer a therapeutic benefit. To assess this possibility, here we first show that tumor growth of proliferating mouse TC-1 HPV-16-associated cancer cells in syngeneic mice becomes accelerated by co-administration of TC-1 or TRAMP-C2 prostate cancer cells made senescent by pre-treatment with the anti-cancer drug docetaxel, or lethally irradiated. Phenotypic analyses of tumor-explanted cells indicated that the observed acceleration of tumor growth was attributable to a protumorigenic environment created by the co-injected senescent and proliferating cancer cells rather than to escape of the docetaxel-treated cells from senescence. Notably, accelerated tumor growth was effectively inhibited by cell immunotherapy using irradiated TC-1 cells engineered to produce interleukin IL-12. Collectively, our data document that immunotherapy, such as the IL-12 treatment, can provide an effective strategy for elimination of the detrimental effects caused by bystander senescent tumor cells in vivo.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2017

Number of the records: 1