E-Poster Presentation 34th Lorne Cancer Conference 2022

Streptococcus pneumoniae potently kill mesothelioma cells in a strain dependent manner (#320)

Hui Juin Shak 1 2 , Kieran T Mulroney 1 , YC Gary Lee 1 2 3
  1. School of Medicine, The University of Western Australia, Perth, WA, Australia
  2. Pleural Medicine Unit, Institute for Respiratory Health, Perth, WA, Australia
  3. Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia

Introduction & Aims: Mesothelioma is a fatal cancer and there is no cure for it. Chemotherapy treatment has shown only minor improvement in survival and current standard treatment is mainly palliative. The use of bacteria or their products presents an attractive approach in mesothelioma as there is strong evidence to suggest that bacterial infection in the pleura may increase survival in these patients. In this preliminary study, we aimed to assess the killing capacity of Streptococcus pneumoniae against mesothelioma cells.

Methods: Clinical S. pneumoniae strains (n= 10) collected from patients with invasive bacterial infection were co-cultured with patient-derived mesothelioma cells (n=9) and benign mesothelial cell line (MeT-5A). S. pneumoniae strains at concentration of 1×107 and 1×104 CFU/mL were added to confluent mesothelioma/mesothelial cells. Cell viability at 0, 4 and 8 hours post infection was assessed by flow cytometry using a Live/Dead cell viability assay.

Results: Our data show a high variability in the mesothelioma/mesothelial cells killing by clinical S. pneumoniae strains, where some strains have a high killing capacity towards some cells, but not the others. For example, on HAM cell line, one bacterial strain killed up to 83% cells while other strain only killed 9.2% of the cells at 4 hours, despite having the same starting inoculum. S. pneumoniae strains increase killing of the five mesothelioma cell lines by median of 1.9 to 9.44-fold over controls at 4 hours, and by 1.67 to 15.19-fold at 8 hours. The fold change varies significantly, between cell lines and bacterial strains.

Conclusion: Understanding the mechanisms underlying the inter-strain variability may provide insight for future therapeutic approaches for mesothelioma.