Mechanistic information about cytokine milieu- activation of tumor-cell TLRs drives the induction of inducible nitric oxide synthase (iNOS) and COX-2, which in turn increase TLR expression and promote a feed-forward loop, leading to tumor progression and the development of more aggressive tumor phenotypes [52]; hence, a strong TLR signal on pathology sections suggests an inflammatory, NF-κB-driven micro-environment rich in prostaglandins and NO. This evidence concerns the gene NFKB1 and neoplasm.