<i>Porphyromonas gingivalis</i> fuels colorectal cancer through CHI3L1-mediated iNKT cell-driven immune evasion
The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). The pathobiont <i>Fusobacterium nucleatum</i> influences the anti-tumor functions of CRC-infiltrating iNKT cells. However, the impact of other bacteria associated with CRC, like <i>Porphyromonas gingivalis</i>, on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated <i>P. gingivalis</i> induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumor microenvironment. Mechanistically, <i>in vivo</i> and <i>in vitro</i> experiments showed that <i>P. gingivalis</i> reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery through increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how <i>P. gingivalis</i> accelerates CRC progression by inducing the upregulation of CHI3L1 in iNKT cells, thus impairing their cytotoxic functions and promoting host tumor immune evasion.
Authors
- Federica Perillo (ORCID: https://orcid.org/0000-0003-3887-1883)
- Yvan Torrente (ORCID: https://orcid.org/0000-0002-2705-3984)
- Michele Ghidini (ORCID: https://orcid.org/0000-0001-5435-1218)
- Ludovica Baldari (ORCID: https://orcid.org/0000-0002-7029-8485)
- Georgia Lattanzi (ORCID: https://orcid.org/0000-0002-1444-2489)
- Maurizio Vecchi (ORCID: https://orcid.org/0000-0003-1558-8604)
- Chiara Amoroso (ORCID: https://orcid.org/0000-0001-6566-9512)
- Andrea Farini (ORCID: https://orcid.org/0000-0002-8514-4921)
- Angélica Díaz‐Basabe (ORCID: https://orcid.org/0000-0003-2096-1223)
- Francesco Strati (ORCID: https://orcid.org/0000-0001-7217-3355)
- Alberto Baeri (ORCID: https://orcid.org/0000-0002-6613-1359)
- Federica Facciotti (ORCID: https://orcid.org/0000-0002-2541-9428)
- Elisa Cassinotti (ORCID: https://orcid.org/0000-0003-3780-6561)
- Flavio Caprioli (ORCID: https://orcid.org/0000-0002-8077-8175)
- Luigi Boni (ORCID: https://orcid.org/0000-0002-5906-3810)
- María Rescigno (ORCID: https://orcid.org/0000-0002-6464-509X)
- Giuseppe Penna (ORCID: https://orcid.org/0000-0003-3534-7090)
Institutions
- Humanitas University (IT)
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Ferrari (Italy) (IT)
- IRCCS Humanitas Research Hospital (IT)
- European Institute of Oncology (IT)
- University of Milano-Bicocca (IT)
Publication Details
- Journal
- Gut Microbes
- Published
- 2024-08-12
- DOI
- https://doi.org/10.1080/19490976.2024.2388801
- Citations
- 42
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 10.10
Funders
- European Commission
- Ministero della Salute
- Ministry of Health, British Columbia
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health