IL-10 mediates sigma₁ receptor-dependent suppression of antitumor immunity

Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma₁ receptor agonists on immune responses in a syngeneic lung cancer model. Sigma₁ 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, sigma₁ 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 sigma₁ receptor antagonists. We report that sigma₁ receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.