Outer Membrane Vesicles from the gut microbiome contribute to tumor immunity by eliciting cross-reactive T cells

Abstract

The gut microbiome plays a key role in cancer immunity. One proposed mechanism is through the elicitation of T cells, which incidentally recognize neo-epitopes arising from cancer mutations (“molecular mimicry (MM)” hypothesis). To support MM, Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA) and orally administered to C57BL/6 mice. The treatment elicited OVA-specific CD8+ T cells in the lamina propria and inhibited the growth of OVA-B16F10 tumors. Importantly, the administration of Outer Membrane Vesicles (OMVs) engineered with different T cell epitopes elicited epitope-specific T cells and inhibited tumor growth. Microbiome shotgun sequencing and TCR sequencing provided evidence that cross-reacting T cells were induced at the mucosal level and subsequently reached the tumor site. Overall, our data support the role of MM in tumor immunity, assign a new role to OMVs and pave the way to new probiotics/OMV-based anti-cancer immunotherapies.

Anti-tumor Efficacy ofin situVaccination Using Bacterial Outer Membrane Vesicles

“…Moreover, Cheng et al chemically associated tumor T cell epitopes to E. coli OMVs and showed that such OMVs protected mice against the challenge with tumors expressing such epitopes 22 . Finally, OMVs expressing specific tumor neo-epitopes either released by intestinal commensal bacteria or administered by oral gavage were shown to protect mice from tumor challenge 18,23 .…”

“…The copyright holder for this preprint (which this version posted April 7, 2023. ; https://doi.org/10.1101/2023.04.07.536036 doi: bioRxiv preprint peptide epitopes elicit anti-tumor immunity [15][16][17][18] . This offers the opportunity to test whether the inclusion of tumor-specific epitopes to the ISV formulation further potentiates the efficacy of ISV.…”