Commensal Bifidobacterium Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines

Abstract

A large body of data both in animals and humans demonstrates that the gut microbiome plays a fundamental role in cancer immunity and in determining the efficacy of cancer immunotherapy. In this work, we have investigated whether and to what extent the gut microbiome can influence the antitumor activity of neo-epitope-based cancer vaccines in a BALB/c-CT26 cancer mouse model. Similarly to that observed in the C57BL/6-B16 model, Bifidobacterium administration per se has a beneficial effect on CT26 tumor inhibition. Furthermore, the combination of Bifidobacterium administration and vaccination resulted in a protection which was superior to vaccination alone and to Bifidobacterium administration alone, and correlated with an increase in the frequency of vaccine-specific T cells. The gut microbiome analysis by 16S rRNA gene sequencing and shotgun metagenomics showed that tumor challenge rapidly altered the microbiome population, with Muribaculaceae being enriched and Lachnospiraceae being reduced. Over time, the population of Muribaculaceae progressively reduced while the Lachnospiraceae population increased—a trend that appeared to be retarded by the oral administration of Bifidobacterium. Interestingly, in some Bacteroidales, Prevotella and Muribaculacee species we identified sequences highly homologous to immunogenic neo-epitopes of CT26 cells, supporting the possible role of “molecular mimicry” in anticancer immunity. Our data strengthen the importance of the microbiome in cancer immunity and suggests a microbiome-based strategy to potentiate neo-epitope-based cancer vaccines.

Chitooligosaccharides Attenuated Hepatic Encephalopathy in Mice through Stabilizing Gut–Liver–Brain Disturbance

“…Growing evidence revealed that Muribaculaceae was enriched by tumor challenge and increased in obese and type 2 diabetes mellitus rats, which was correlated with glucose and lipid metabolisms and immunoreaction. [ 49–51 ] Moreover, it was positively related with proinflammatory metabolites and systemic inflammation, [ 52 ] which is basically consistent with the results of this study. However, previous studies have been suggested that Muribaculaceae as probiotics is involved in gut microbial remodeling and disease alleviation, [ 53 ] indicating that the role of Muribaculaceae is extremely intricate and should be separately discussed in specific situations.…”

Microbiome-based interventions to modulate gut ecology and the immune system

“…Another method is that the microbiota can enhance vaccine response via activation of convergent pathways, leading to a greater response than the vaccine would cause alone. • The application of probiotic bifidobacteria has been shown to enhance the immune response to a neoepitope-based cancer vaccine 293 . This was suggested to be caused by the probiotic leading to an increase in taxa with high sequence similarity to the neoepitope, leading to further immune stimulation.…”

“…• The application of probiotic bifidobacteria has been shown to enhance the immune response to a neoepitope-based cancer vaccine 293 . This was suggested to be caused by the probiotic leading to an increase in taxa with high sequence similarity to the neoepitope, leading to further immune stimulation.…”

The Crosstalk Between Microbiome, Cancer Immunology, and Immunotherapeutics: Myth or Reality

“…There is growing evidence that the variety and composition of gut bacteria influence the therapeutic efficacy of various cancer treatments [19,[34][35][36][37][38][39][40][41]. In 1910, Coley WB, for the first time, injected streptococcal organisms into a patient suffering from unresectable sarcoma, resulting in excellent antitumor responses [42].…”