DOAJ Open Access 2022

Outer Membrane Vesicles From The Gut Microbiome Contribute to Tumor Immunity by Eliciting Cross-Reactive T Cells

Michele Tomasi Elena Caproni Mattia Benedet Mattia Benedet Ilaria Zanella +28 lainnya

Abstrak

A growing body of evidence supports the notion that the gut microbiome plays an important role in cancer immunity. However, the underpinning mechanisms remain to be fully elucidated. One attractive hypothesis envisages that among the T cells elicited by the plethora of microbiome proteins a few exist that incidentally recognize neo-epitopes arising from cancer mutations (“molecular mimicry (MM)” hypothesis). To support MM, the human probiotic Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA-E.coli Nissle) and orally administered to C57BL/6 mice. The treatment with OVA-E.coli Nissle, but not with wild type E. coli Nissle, induced OVA-specific CD8+ T cells and inhibited the growth of tumors in mice challenged with B16F10 melanoma cells expressing OVA. The microbiome shotgun sequencing and the sequencing of TCRs from T cells recovered from both lamina propria and tumors provide evidence that the main mechanism of tumor inhibition is mediated by the elicitation at the intestinal site of cross-reacting T cells, which subsequently reach the tumor environment. Importantly, the administration of Outer Membrane Vesicles (OMVs) from engineered E. coli Nissle, as well as from E. coli BL21(DE3)ΔompA, carrying cancer-specific T cell epitopes also elicited epitope-specific T cells in the intestine and inhibited tumor growth. Overall, our data strengthen the important role of MM in tumor immunity and assign a novel function of OMVs in host-pathogen interaction. Moreover, our results pave the way to the exploitation of probiotics and OMVs engineered with tumor specific-antigens as personalized mucosal cancer vaccines.

Topik & Kata Kunci

Neoplasms. Tumors. Oncology. Including cancer and carcinogens

Penulis (33)

Michele Tomasi

Elena Caproni

Mattia Benedet

Ilaria Zanella

Sebastiano Giorgetta

Mattia Dalsass

Enrico König

Assunta Gagliardi

Laura Fantappiè

Alvise Berti

Silvia Tamburini

Lorenzo Croia

Gabriele Di Lascio

Erika Bellini

Silvia Valensin

Giada Licata

Guido Sebastiani

Francesco Dotta

Federica Armanini

Fabio Cumbo

Francesco Asnicar

Aitor Blanco-Míguez

Eliana Ruggiero

Nicola Segata

Guido Grandi

Alberto Grandi

Format Sitasi

APA MLA BibTeX

Tomasi, M., Caproni, E., Benedet, M., Benedet, M., Zanella, I., Giorgetta, S. et al. (2022). Outer Membrane Vesicles From The Gut Microbiome Contribute to Tumor Immunity by Eliciting Cross-Reactive T Cells. https://doi.org/10.3389/fonc.2022.912639

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Informasi Jurnal

Tahun Terbit: 2022
Sumber Database: DOAJ
DOI: 10.3389/fonc.2022.912639
Akses: Open Access ✓