A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Alistipes and Eggerthella shape the response to oncolytic adenovirus therapy in mice and humans through short-chain fatty acid metabolism
Tekijät: van der Heijden, Mirte; Armstrong Clubb, James Hugo; Erawijantari, Pande Putu; Ronkainen, Aki; Arias, Victor; Jirovec, Elise; Kudling, Tatiana; Pakola, Santeri Artturi; Ojala, Nea; Haybout, Lyna; Basnet, Saru; Grönberg-Vähä-Koskela, Susanna; Raatikainen, Sini Karoliina; Hemminki, Otto; Kanerva, Anna; Alves Quixabeira, Dafne Carolina; Cervera-Carrascon, Victor; dos Santos, João Manuel; Lahti, Leo; Hemminki, Akseli
Julkaisuvuosi: 2026
Lehti: OncoImmunology
Artikkelin numero: 2656514
Vuosikerta: 15
Numero: 1
ISSN: 2162-4011
eISSN: 2162-402X
DOI: https://doi.org/10.1080/2162402X.2026.2656514
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1080/2162402x.2026.2656514
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/522993573
Rinnakkaistallenteen lisenssi: CC BY NC
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
Accumulating evidence implicates the microbiome as an important determinant of clinical outcomes in cancer therapies; however, the role of the microbiome in oncolytic virus therapy remains largely unexplored. We investigated the gut microbiome of cancer patients following treatment with the oncolytic adenovirus igrelimogene litadenorepvec (Ad5/3-E2F-d24-hTNF-IRES-hIL2; TILT-123). Baseline fecal samples from phase I clinical trials (NCT04695327 and NCT05271318) were analyzed using shotgun metagenomic sequencing and compared to treatment outcomes. A higher relative abundance of Alistipes was observed in patients with treatment benefit, while elevated Eggerthella was observed with reduced benefit. These associations were validated in a preclinical mouse model where administration of Alistipes shahii improved the efficacy of adenovirus therapy. In addition, enrichment analysis in patient samples showed a positive correlation between higher relative abundance of Alistipes and elevated short-chain fatty acids in both feces and serum, which in turn revealed higher circulating neutrophil counts. Finally, in a case study, we observed that adenovirus treatment resulted in increased Alistipes relative abundance and reduced Eggerthella relative abundance, indicating that adenovirus therapy may beneficially modulate the microbiome. Overall, our findings reveal a novel association between Alistipes, Eggerthella, and the therapeutic response to oncolytic adenovirus therapy, highlighting their potential as biomarkers or targets for microbiome-based interventions such as pre-, pro-, or postbiotics.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
This study was supported by iCANDOC Doctoral Education Pilot in Precision Cancer Medicine (PCM, University of Helsinki); Cancer Foundation Finland; Sigrid Juselius Foundation; Jane and Aatos Erkko Foundation; EU Horizon Grant 811693 (UNLEASHAD); Finnish Cultural Foundation; EU Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No. 813453; TILT Biotherapeutics Ltd.; HUCH Research Funds; K. Albin Johansson Foundation; Selma and Maja-Lisa Selander’s Fund for Research in Odontology; Ida Montin Foundation; Finnish Red Cross Blood Service; Department of Defense. We thank Albert Ehrnrooth and Karl Fazer for their generous research support. Open Access funding was provided by the University of Helsinki.
