Bacillus Calmette-Guérin and anti-PD-L1 combination therapy boosts immune response against bladder cancer

OncoTargets and Therapy
Yonghua WangHaitao Niu

Abstract

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. 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. 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 mye...Continue Reading

Citations

Aug 28, 2020·Asia-Pacific Journal of Clinical Oncology·Darren Ming-Chun Poon
Sep 11, 2019·Nature Reviews. Urology·Anna K SchneiderLaurent Derré
Jan 16, 2021·The Urologic Clinics of North America·Sujit S NairAshutosh K Tewari
Mar 7, 2021·Journal of Clinical Medicine·Renate PichlerMartin Thurnher
Apr 4, 2021·International Journal of Molecular Sciences·Florus C de JongDan Theodorescu
Jun 26, 2021·Urologic Oncology·Neal D ShoreGary D Steinberg
Jun 26, 2021·Expert Opinion on Investigational Drugs·Irbaz Bin RiazSyed A Hussain
Oct 14, 2021·Scientific Reports·Leandro Carvalho Dantas BredaSandro Rogério de Almeida
Oct 31, 2021·Journal of Hematology & Oncology·Yang XunHua You

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Methods Mentioned

BETA
flow cytometry
density gradient centrifugation
transgenic
surgical resection

Clinical Trials Mentioned

NCT02792192
NCT02324582
NCT02808143

Software Mentioned

Prism
GraphPad
CellQuest

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