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Published on: September 2, 2014
IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity
Li X Zhu1, Sherven Sharma, Brian Gardner
1University of California Los Angeles Lung Cancer Research Program, Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095-1690, USA.
Abstract:
Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma(1) receptor agonists on immune responses in a syngeneic lung cancer model. Sigma(1) receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma(1) receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma(1) receptor antagonists. We report that sigma(1) receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.
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