Increased Fusobacterium tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcome

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dc.contributor.authorDuggan, William P.en
dc.contributor.authorSalvucci, Manuelaen
dc.contributor.authorKisakol, Batuhanen
dc.contributor.authorLindner, Andreas U.en
dc.contributor.authorReynolds, Ian S.en
dc.contributor.authorDussmann, Heikoen
dc.contributor.authorFay, Joannaen
dc.contributor.authorO'Grady, Tonyen
dc.contributor.authorLongley, Daniel B.en
dc.contributor.authorGinty, Fionaen
dc.contributor.authorMcDonough, Elizabethen
dc.contributor.authorSlade, Daniel J.en
dc.contributor.authorBurke, John P.en
dc.contributor.authorPrehn, Jochen H. M.en
dc.date.accessioned2024-01-18T19:54:25Zen
dc.date.available2024-01-18T19:54:25Zen
dc.date.issued2023-07en
dc.description.abstractAbstract: There is currently an urgent need to identify factors predictive of immunogenicity in colorectal cancer (CRC). Mucinous CRC is a distinct histological subtype of CRC, associated with a poor response to chemotherapy. Recent evidence suggests the commensal facultative anaerobe Fusobacterium may be especially prevalent in mucinous CRC. The objectives of this study were to assess the association of Fusobacterium abundance with immune cell composition and prognosis in mucinous CRC. Our study included two independent colorectal cancer patient cohorts, The Cancer Genome Atlas (TCGA) cohort, and a cohort of rectal cancers from the Beaumont RCSI Cancer Centre (BRCC). Multiplexed immunofluorescence staining of a tumour microarray (TMA) from the BRCC cohort was undertaken using Cell DIVE technology. Our cohorts included 87 cases (13.3%) of mucinous and 565 cases (86.7%) of non-mucinous CRC. Mucinous CRC in the TCGA dataset was associated with an increased proportion of CD8 + lymphocytes (p = 0.018), regulatory T-cells (p = 0.001) and M2 macrophages (p = 0.001). In the BRCC cohort, mucinous RC was associated with enhanced CD8 + lymphocyte (p = 0.022), regulatory T-cell (p = 0.047), and B-cell (p = 0.025) counts. High Fusobacterium abundance was associated with an increased proportion of CD4 + lymphocytes (p = 0.031) and M1 macrophages (p = 0.006), whilst M2 macrophages (p = 0.043) were under-represented in this cohort. Patients with increased Fusobacterium relative abundance in our mucinous CRC TCGA cohort tended to have better clinical outcomes (DSS: likelihood ratio p = 0.04, logrank p = 0.052). Fusobacterium abundance may be associated with improved outcomes in mucinous CRC, possibly due to a modulatory effect on the host immune response. Key messages: • Increased Fusobacterium relative abundance was not found to be associated with microsatellite instability in mucinous CRC. • Increased Fusobacterium relative abundance was associated with an M2/M1 macrophage switch, which is especially significant in mucinous CRC, where M2 macrophages are overexpressed. • Increased Fusobacterium relative abundance was associated with a significant improvement in disease specific survival in mucinous CRC. • Our findings were validated at a protein level within our own in house mucinous and non-mucinous rectal cancer cohorts.en
dc.description.versionPublished versionen
dc.format.extentPages 829-841en
dc.format.extent13 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1007/s00109-023-02324-5en
dc.identifier.eissn1432-1440en
dc.identifier.issn0946-2716en
dc.identifier.issue7en
dc.identifier.orcidSlade, Daniel [0000-0001-5634-7220]en
dc.identifier.other10.1007/s00109-023-02324-5 (PII)en
dc.identifier.pmid37171483en
dc.identifier.urihttps://hdl.handle.net/10919/117396en
dc.identifier.volume101en
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/37171483en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMucinous colorectal canceren
dc.subjectFusobacteriumen
dc.subjectMicrosatellite instabilityen
dc.subject.meshMacrophagesen
dc.subject.meshHumansen
dc.subject.meshFusobacteriumen
dc.subject.meshColorectal Neoplasmsen
dc.subject.meshRectal Neoplasmsen
dc.subject.meshMicrosatellite Instabilityen
dc.titleIncreased <i>Fusobacterium</i> tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcomeen
dc.title.serialJournal of Molecular Medicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2023-04-19en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen

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