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

Tomasi, M.; Caproni, E.; Benedet, M.; Zanella, I.; Giorgetta, S.; Dalsass, M.; Koenig, E.; Gagliardi, A.; Fantappie', L.; Berti, A.; Tamburini, S.; Croia, L.; Di Lascio, G.; Bellini, E.; Valensin, S.; Licata, G.; Sebastiani, G.; Dotta, F.; Armanini, F.; Cumbo, F.; Asnicar, F.; Blanco-Miguez, A.; Ruggiero, E.; Segata, N.; Grandi, A.; Grandi, G.

doi:10.1101/2021.11.05.467432

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bioRxiv · 10.1101/2021.11.05.467432

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

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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.

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Tomasi, M., Caproni, E., Benedet, M., Zanella, I., Giorgetta, S., Dalsass, M., Koenig, E., Gagliardi, A., Fantappie', L., Berti, A., Tamburini, S., Croia, L., Di Lascio, G., Bellini, E., Valensin, S., Licata, G., Sebastiani, G., Dotta, F., Armanini, F., Cumbo, F., Asnicar, F., Blanco-Miguez, A., Ruggiero, E., Segata, N., Grandi, A., Grandi, G.. 2021-11-05. Outer Membrane Vesicles from the gut microbiome contribute to tumor immunity by eliciting cross-reactive T cells. https://doi.org/10.1101/2021.11.05.467432

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