Data from Activation of Toll-like Receptor 4 on Tumor Cells <i>In vitro</i> Inhibits Subsequent Tumor Growth <i>In vivo</i>

Abstract

<div>Abstract<p>Although an eruption of information on the role of Toll-like receptor 4 (TLR4), the main receptor for bacterial lipopolysaccharide, in activating macrophages and dendritic cells has emerged, very little is known about the role of TLR4 present on epithelial cells from sterile environments like tumors. The main goal of this work was to investigate the consequences of TLR4 activation present on tumor cells in two different animal models of cancer: the Dunning rat prostate cancer and the B16 murine melanoma models. We show that (<i>a</i>) activating TLR4 signaling in two different tumor cell lines <i>in vitro</i> modifies the tumor outgrowth <i>in vivo</i>; (<i>b</i>) this effect is not due to a direct consequence of TLR4 signaling on the proliferation/apoptosis balance of the tumor cells; (<i>c</i>) the T-cell compartment is somehow involved in the described phenomenon because the inhibitory effect observed is not seen in athymic nude mice; and (<i>d</i>) tumor-infiltrating lymphocytes purified from tumors induced by TLR4-activated cells show strong induction of IFNγ transcript in detriment of interleukin-10 transcript, suggesting a change in their functionality. We hypothesize that TLR4 signaling in tumor cells <i>in vitro</i> induces the expression of proinflammatory mediators, which could dramatically alter the maturation state of dendritic cells present at the site of inoculation, switching the type of immune response elicited against the tumor. These results open up new avenues for understanding the role of TLR4 in tumor cells and for identifying potential new therapy strategies for cancer. [Cancer Res 2007;67(21):10519–27]</p></div>