Mebendazole stimulates CD14+ myeloid cells to enhance T-cell activation and tumour cell killing

// Jenny Rubin 1 , Sharmineh Mansoori 1 , Kristin Blom 1 , Malin Berglund 1 , Lena Lenhammar 1 , Claes Andersson 1 , Angelica Loskog 2 , Marten Fryknas 1 , Peter Nygren 2 and Rolf Larsson 1 1 Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, SE-75185, Sweden 2 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SE-75185, Sweden Correspondence to: Rolf Larsson, email: rolf.larsson@medsci.uu.se Keywords: mebendazole; immune activation; drug repositioning; cancer Received: May 07, 2018      Accepted: June 13, 2018      Published: July 20, 2018 ABSTRACT Mebendazole (MBZ) was recently shown to induce a tumor suppressive M1 phenotype in THP-1 monocytes and macrophages. In the present study the immune effects of MBZ was further investigated using human peripheral blood mononuclear cells (PBMCs) co-cultured with tumour cells. The Biomap platform was used to screen for biomarkers induced from MBZ exposed co-cultures of T-cell receptor activated PBMCs, HT29 colon cancer cells and either human fibroblasts or human umbilical vein endothelial cells (HUVEC) cells. In these co-culture systems MBZ at 0.3-10 μM induced significant increases in TNFα and IFNγ indicating immune stimulation. PBMC cultures alone were subsequently tested for activation status and only in PBMCs activated by CD3/IL2 stimulation and MBZ, at a clinically achievable concentration, was able to increase PBMC clustering and release of pro-inflammatory IFNγ, TNFα, IL6 and IL1β cytokines. Moreover, when PBMC cultures were functionally tested for immune cell killing of lung cancer A549NucLightRed cells, MBZ significantly increased tumour cell apoptosis and reduced the number of surviving tumour cells. This effect was dependent on the presence of CD14 monocytes/macrophages in the co-culture. In summary, MBZ potentiated the immune stimulatory and anticancer effects of anti-CD3/IL2 activated PBMCs which could be relevant to explain the anticancer activity of MBZ observed in the clinic.