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10.2147/OTT.S165840

http://scihub22266oqcxt.onion/10.2147/OTT.S165840
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C5962256!5962256!29844686
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suck abstract from ncbi


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pmid29844686      Onco+Targets+Ther 2018 ; 11 (ä): 2891-9
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  • Bacillus Calmette?Guérin and anti-PD-L1 combination therapy boosts immune response against bladder cancer #MMPMID29844686
  • Wang Y; Liu J; Yang X; Liu Y; Liu Y; Li Y; Sun L; Yang X; Niu H
  • Onco Targets Ther 2018[]; 11 (ä): 2891-9 PMID29844686show ga
  • Background: Programmed death-ligand 1 (PD-L1) is a critical immune checkpoint molecule which promotes immunosuppression by binding to PD-1 on T-cells in tumor immunity. We have previously identified that activation of toll like receptor 4 (TLR-4), which serves an important role in the induction of antitumor immune response during Bacillus Calmette?Guérin (BCG) immunotherapy, could upregulate PD-L1 expression in bladder cancer (BCa) cells through the classical mitogen-activated protein kinase (MAPK) pathway and subsequently weaken the cytotoxicity of cytotoxic T lymphocyte (CTL). It is, therefore, necessary to investigate the possible potential relationship between PD-L1 expression and BCG immunotherapy. Materials and methods: In this study we investigated the effects of BCG treatment on PD-L1 expression in BCa cells and also evaluated the efficacy of BCG and anti-PD-L1 combination therapy in immunocompetent orthotopic rat BCa models. Results: We found that PD-L1 expression was obviously upregulated in BCa cells in response to BCG treatment both in vitro and in vivo. Moreover, BCG and anti-PD-L1 combination treatment activated a potent antitumor immune response with the increase in the number and activity of tumor-infiltrating CD8+ T cells, as well as the reduction in myeloid-derived suppressor cells (MDSCs), and eventually elicits prominent tumor growth inhibition and prolonged survival, and was found to be much more effective than either agent alone. Conclusion: These findings highlight the adaptive dynamic regulation of PD-L1 in response to BCG immunotherapy and suggest that combination of BCG immunotherapy with PD-L1 blockade may be an effective antitumor strategy for improving treatment outcomes of BCa.
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