Prostate Cancer-Induced Remodeling of the Topologies and Interplay of the TLR (Toll-Like Receptor) and Chemokine Signaling Pathways

Toll-like receptor (TLR) signaling pathway is part of the innate immune program that might destroy the cancer cells within a tissue if properly activated and the malignant cells’ defense system is inhibited. Activation of the TLR pathway induces production of pro-inflammatory cytokines and upregulation of costimulatory molecules, impacting initiation, advancement, and control of cancers by regulating the inflammatory microenvironment. Publicly accessible transcriptomic profiles of three cancer nodules and the surrounding normal tissue isolated from a surgically removed prostate tumor were used to determine the cancer-induced alterations of the TLR and chemokine (CHS) signaling pathways, and their interplay. Our analysis revealed that the deep cancer-related topology remodeling is different not only between patients but even between equally graded cancer nodules within the same tumor. We found also that cancer reorganized the transcriptomic networks interconnecting the two pathways via their shared genes, inducing novel expression coordination while removing others. The reorganization was different among the cancer nodules, indicating distinct changes in the molecular mechanisms of the immune response and the need to personalize the anti-cancer treatment beyond the patient him/herself to the main cancer nodules in the tumor.