Enhanced Acid Sphingomyelinase Activity Drives Immune Evasion and Tumor Growth in Non-Small Cell Lung Carcinoma.

Abstract

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. Cancer Res; 77(21); 5963-76. ©2017 AACR.

DOI: 10.1158/0008-5472.CAN-16-3313

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Cite this paper

@article{Kachler2017EnhancedAS, title={Enhanced Acid Sphingomyelinase Activity Drives Immune Evasion and Tumor Growth in Non-Small Cell Lung Carcinoma.}, author={Katerina Kachler and Maximilian Bailer and Lisanne Heim and Fabian Schumacher and Martin Reichel and Corinna D Holzinger and Sonja Trump and Susanne Mittler and Juliana M. Monti and Denis Iulian Trufa and Ralf J. Rieker and Arndt Hartmann and Horia S{\^i}rbu and Burkhard Kleuser and Johannes Kornhuber and Susetta Finotto}, journal={Cancer research}, year={2017}, volume={77 21}, pages={5963-5976} }