Pre-existing fas ligand (FasL) in cancer cells elicits tumor-specific protective immunity, but delayed induction of FasL expression after inoculation facilitates tumor formation

Overexpression of Fas ligand (FasL) in cancer cells elicits potential antitumor effects via recruitment of neutrophils. Conversely, FasL‐expressing tumors may counterattack tumor‐infiltrating lymphocytes by delivering apoptotic death signals via Fas/FasL interactions, which may lead to tumor escape....

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Bibliographic Details
Published in:Molecular carcinogenesis 2013-09, Vol.52 (9), p.705-714
Main Authors: Chiu, Hsiao-Ying, Sun, Guang-Huan, Chen, Shiow-Yi, Wang, Hsiao-Hsien, Ho, Ming-Yi, Chu, Chia-Yi, Wu, Wan-Lin, Jhou, Ren-Shiang, Tsai, Yi-Lin, Huang, Rui-Ting, Sun, Kuang-Hui, Tang, Shye-Jye
Format: Article
Language:English
Subjects:
Animals
antitumor
Cell Line, Tumor
Cell Transformation, Neoplastic - drug effects
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - immunology
Cell Transformation, Neoplastic - metabolism
Doxycycline - pharmacology
Fas ligand
Fas Ligand Protein - biosynthesis
Fas Ligand Protein - genetics
Fas Ligand Protein - immunology
Fas Ligand Protein - metabolism
Humans
Jurkat Cells
lung cancer
Male
Melanoma, Experimental - genetics
Melanoma, Experimental - immunology
Melanoma, Experimental - metabolism
Melanoma, Experimental - pathology
Mice
Mice, Inbred C57BL
microenvironment
tumor escape
Tumor Microenvironment - drug effects
Tumor Microenvironment - genetics
Tumor Microenvironment - immunology
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Summary:Overexpression of Fas ligand (FasL) in cancer cells elicits potential antitumor effects via recruitment of neutrophils. Conversely, FasL‐expressing tumors may counterattack tumor‐infiltrating lymphocytes by delivering apoptotic death signals via Fas/FasL interactions, which may lead to tumor escape. In order to distinguish the role of FasL in antitumor activity and tumor progression, Lewis lung carcinoma cells (LLC‐1) were used to establish the cell line LLC‐FasL, in which FasL expression was repressed by doxycycline (Dox) treatment and induced in the absence of Dox. LLC‐FasL cells promote tumor regression when expressing FasL, whereas tumor outgrowth is observed by depletion of FasL expression. To investigate whether initial expression of FasL during tumor formation is critical for FasL‐mediated tumor regression, Dox‐treated LLC‐FasL cells were inoculated into Dox‐treated mice, but Dox treatment was stopped 5 days after inoculation. When low cell numbers were inoculated, we observed 80% survival and no tumor formation, whereas no mice survived inoculation with high cell numbers, despite the delayed induction of FasL by Dox withdrawal. The inoculation of a high density of cells may establish a favorable tumor microenvironment before the expression of FasL. Our findings demonstrate that FasL may elicit antitumor activity when it is initially present on injected cancer cells and thus can act prior to tumor microenvironment formation. Furthermore, a well‐established tumor microenvironment abrogates FasL‐mediated antitumor activity. © 2012 Wiley Periodicals, Inc.
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.21909