Back to basics: bacteria-based immunotherapy using Salmonella for melanoma treatment

Abstract

Among skin cancers, melanoma is the most lethal type, with a low 5-year overall survival rate in metastatic patients. Additionally, it shows an increasing incidence in young population. Bacteria-based immunotherapies offer unique advantages in the fight against melanoma, since this tumor is highly immunogenic. Unlike conventional cancer treatments, which have limited tumor specificity, bacteria as Salmonella selectively colonize tumors and kill cancer cells, through diverse mechanisms. In this work we aim to dissect the changes in melanoma cell proteins after Salmonella LVR01 infection through mass spectrometry. Proteomic analysis comparing non-infected (control) vs infected melanoma cells identified 2269 eukaryotic proteins, being 2173 in control samples and 2067 in infected cells. Furthermore, 1971 proteins were identified in both conditions, being 202 and 96 proteins exclusively identified in control or infected cells, respectively. Relative abundance analyses showed 32 proteins overrepresented in infected samples (enriched proteins, EP) and 64 proteins overrepresented in the control group (repressed proteins, RP). For EP, there was an increase in biological processes corresponding to response to stimuli and cell proliferation and growth, while enrichment in molecular functions as nucleic acid binding and electron transfer activity, among others. Conversely, for the RP we observed enrichment in biological processes related to regulation and cellular component organization and localization. Regarding molecular functions, we found enrichment in protein binding and hydrolase activity. Three separate pathways of interaction were overrepresented, corresponding to mRNA processing, keratinization and energy production. Interestingly, the latter was overrepresented in both EP and RP datasets, suggesting that Salmonella infection might influence cancer metabolism. Candidates were then contrasted with existing literature, including their use as prognostic markers in diverse types of cancer, and protein expression changes were further confirmed by RT-qPCR. In this way, we obtained new candidate molecules that could explain the antitumor activity exhibited by Salmonella LVR01.