The local tumour immune response following systemic Salmonella enterica serovar Typhimurium infection

Sile Ann Johnson
2018
In recent years, there is renewed interest in the potential of bacteria as an alternative cancer therapeutic strategy. Salmonella enterica serovar Typhimurium is arguably the most well studied strain of bacteria for cancer therapy, examined in both pre-clinical and clinical settings. Many of the studies which have demonstrated a role for S. Typhimurium in tumour growth inhibition or regression have focused on increasing the tumour-specific localisation of the bacteria, or enhancing the efficacy
more » ... ancing the efficacy of the treatment modality. However, the exact mechanisms underlying S. Typhimurium-mediated tumour growth inhibition are incompletely elucidated, particularly with respect to the myeloidderived immune cells, such as monocytes and macrophages. The current study intended to address the dearth of information in the literature pertaining to the overall tumour-local immune response to systemically administered S. Typhimurium. This was achieved through the development of an in vivo tumour model and the optimisation of the S. Typhimurium administration protocol to maximise therapeutic effect. This allowed for the investigation of changes in multiple immune cell types in the tumour, both in number and functional phenotype, following infection. It was found that following systemic SL7207 infection, there was an increase in the secretion of pro-inflammatory mediators in the tumour milieu. This was accompanied by the activation of both neutrophils and monocytes, and possibly increased migration of tumour-associated dendritic cells. Interestingly, we found evidence to suggest that resident tumour-associated macrophages (TAMs) do not participate in mediating the pro-inflammatory tumour microenvironment following infection, which is suggested in some published reports. We were also interested in the types of T cell responses stimulated in the tumour following infection. This investigation revealed increases in the frequency of tumour-associated T helper (TH)1, but also TH17 cells following infection. There was also a concomitant decreas [...]
doi:10.5525/gla.thesis.8982 fatcat:pyeaisioerdmxhentn7uftihpy