Expression of TLR4 and major inflammatory cytokines in patients with bladder cancer of different grade and stage

Abstract

Summary. Background: The bladder cancer is immunogenic, and neoantigens generated by tumor cells trigger a notable immune response in the host. On the other hand, multiple immune escape mechanisms allow for avoiding the recognition by the host immune system. Toll-like receptor type 4 and inflammatory cytokines play major role in the immune response to bladder cancer. Aim: To assess the expression of TLR4 and the genes of major inflammatory cytokines in tumor cells and in unaffected tissue of the bladder. Materials and Methods: The pairs of samples from the urinary bladder tumor and unaffected adjacent tissue were obtained from 50 surgically treated patients with bladder cancer. The level of expression of TLR4, TGF-β1, INF-γ, TNF-α genes was evaluated by real-time polymerase chain reaction. Results: Bladder cancer cells are characterized by lower expression levels of TLR4, TGF-β1, INF-γ, TNF-α as compared to unaffected tissue. In patients with recurrent cancer, expression of TLR-4 and cytokines does not change both in tumor and in unaffected tissue of the bladder. Expression of TLR4 is identically low both in low- and high-grade cancer. Expression levels of the INF-γ and TNF-α are remarkably low in muscle-invasive cancer compared to the unaffected bladder tissue. The level of TGF-β1 in bladder cancer is comparable to the unaffected tissue of the bladder, while in the intact and metastatic lymph nodes it is significantly upregulated. Conclusion: Bladder cancer tissue differs from the unaffected part of the bladder wall in the level of TLR4, TGF-β1, INF-γ, TNF-α expression.