TY  - JOUR
A1  - Kachler, Katerina
A1  - Bailer, Maximilian
A1  - Heim, Lisanne
A1  - Schumacher, Fabian
A1  - Reichel, Martin
A1  - Holzinger, Corinna D.
A1  - Trump, Sonja
A1  - Mittler, Susanne
A1  - Monti, Juliana
A1  - Trufa, Denis I.
A1  - Rieker, Ralf J.
A1  - Hartmann, Arndt
A1  - Sirbu, Horia
A1  - Kleuser, Burkhard
A1  - Kornhuber, Johannes
A1  - Finotto, Susetta
T1  - Enhanced acid sphingomyelinase activity drives immune evasion and tumor growth in non-small cell lung carcinoma
JF  - Cancer research
N2  - The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal therapeutic target. In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non-small cell lung cancer (NSCLC). RNAi-mediated attenuation of SMPD1 in human NSCLC cells rendered them resistant to serum starvation-induced apoptosis. In a murine model of lung adenocarcinoma, ASM deficiency reduced tumor development in a manner associated with significant enhancement of Th1-mediated and cytotoxic T-cell-mediated antitumor immunity. Our findings indicate that targeting ASM in NSCLC can act by tumor cell-intrinsic and-extrinsic mechanisms to suppress tumor cell growth, most notably by enabling an effective antitumor immune response by the host. (C) 2017 AACR.
Y1  - 2017
U6  - https://doi.org/10.1158/0008-5472.CAN-16-3313
SN  - 0008-5472
SN  - 1538-7445
VL  - 77
IS  - 21
SP  - 5963
EP  - 5976
PB  - American Association for Cancer Research
CY  - Philadelphia
ER  -