Toll-like receptors and prostate cancer

Abstract

Prostate cancer is the second leading cause of cancer-related death in men after lung cancer. Immune responses clearly play a critical role in the tumorigenesis and in the efficacy of radiation therapy and chemotherapy in prostate cancer; however, the underlying molecular mechanisms are still poorly understood. Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors that play a key role in host immune system. Recent studies demonstrate that there are links between TLRs and cancer; however, the function and biological importance of TLRs in prostate cancer seems complex. To elucidate the role of TLRs and innate immunity in prostate cancer might provide us with a better understanding of the molecular mechanisms of this disease. Moreover, utilizing the agonists or antagonists of TLRs might represent a promising new strategy against prostate cancer. In this review, we summarize recent advances on the studies of association between TLR signaling and prostate cancer, TLR polymorphisms and prostate cancer risk, and provide some insights about TLRs as potential targets for prostate cancer immunotherapy.

Keywords: TLR signaling; immunotherapy; innate immunity; prostate cancer; toll-like receptor.

Figure 1

Toll-like receptors and TLR-mediated signaling pathway. TLR1 and TLR6 recognize their ligands as heterodimers with TLR2. For TLR4, MD2, and CD14 are required for LPS recognition and signaling. TLR3, TLR4, TLR5, TLR7, and TLR9 are currently thought to deliver their signal by forming homodimers after interacting with their ligands. TLR3, TLR7/8, and TLR9 are intracellular TLRs and are involved in the recognition of nucleic acids. Most TLRs, except for TLR3, signal through MyD88 pathway to activate NF-κB and AP1. TLR3 and TLR4 can signal through MyD88-independent pathway (TRIF pathway) to activate INF-β.

Figure 2

Toll-like receptors and prostate cancer. TLR activation in tumor cells and its activation in tumor microenvironment such as in typical innate immune cells lead to a complex scenario, which determines the role of TLRs in prostate cancer development. The activation of TLRs in antigen-presenting cells, such as DCs, macrophages, and B cells, can lead to either Th1 and T cytotoxic responses or Th2 and Treg responses. The activations of TLR2, 4, and 9 in prostate cancer cells appear to promoter tumor growth, but the activation of TLR3, 4, 5, and 7 might inhibit prostate cancer.