Building a Bridge between Chemotherapy and Immunotherapy in Malignant Pleural Mesothelioma: Investigating the Effect of Chemotherapy on Immune Checkpoint Expression

International Journal of Molecular Sciences

卷:20

Patrick Pauwels¹  Julie Jacobs¹  Jorrit De Waele¹  EvelienLJ Smits¹  Glenn Cavents¹  JonasRM Van Audenaerde¹  Jinthe Van Loenhout¹  Elly Marcq¹  JanP van Meerbeeck¹ 

[1] Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium;

关键词: chemotherapy;    tumor microenvironment;    mesothelioma;    immune checkpoints;    MPM;    PD-1;    PD-L1;    TIM-3;    LAG-3;   

DOI  :  10.3390/ijms20174182

来源: DOAJ

【 摘 要 】

In light of the promising results of immune checkpoint blockade (ICPB) in malignant pleural mesothelioma (MPM), we investigated the effect of different chemotherapeutic agents on the expression of immune checkpoints (ICPs) in order to rationally design a good treatment schedule for their combination with ICP blocking antibodies. Cisplatin, oxaliplatin and pemetrexed are interesting chemotherapeutic agents to combine with immunotherapy given their immunomodulatory capacities. We looked into cisplatin and pemetrexed because their combination is used as first-line treatment of MPM. Additionally, the effect of the immunogenic chemotherapeutic agent, oxaliplatin, was also studied. Three different MPM cell lines were used for representation of both epithelioid and sarcomatoid subtypes. The desired inhibitory concentrations of the chemotherapeutic agents were determined with the SRB-assay. Allogeneic co-cultures of MPM cells with healthy donor peripheral blood mononuclear cells (PBMC) were set up to assess the effect of these chemotherapeutic agents on the expression of ICPs (PD-1, LAG-3, TIM-3) and their ligands (PD-L1, PD-L2, galectin-9). Cisplatin might be a promising treatment to combine with ICP blocking antibodies since our MPM cell lines were most susceptible to this stand-alone treatment. We found that the expression of ICPs and their ligands on both MPM cells and PBMC was mostly downregulated or unaltered when treated with chemotherapeutic agents, though no clear trend could be determined.

【 授权许可】

Unknown