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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1553034
This article is part of the Research Topic Microbiota-Immune Interactions: A New Frontier in Cancer Treatment Optimization View all 5 articles
Patient-derived pancreatic tumor bacteria exhibit oncogenic properties and are recognized by MAIT cells in tumor spheroids
Provisionally accepted
Poojabahen Tajpara 1
Michał Jacek Sobkowiak 2
Katie Healy 1
Sabrina NAUD 3
Beate Gündel 3
Asif Halimi 4 Zara Ahmad Khan 1
Giorgio Gabarrini 3
Sylvie Le Guyader 5 Gabriela Imreh 5
Julie Reisz Haines 6 Marco Del Chiaro 6
Angelo D'Alessandro 6
Rainer Heuchel 3
Matthias Löhr 3 Volkan Özenci 1
Margaret Sällberg Chen 1*- 1 Department of Laboratory Medicine, Karolinska Institutet (KI), Solna, Stockholm, Sweden
- 2 Department of Dental Medicine, Karolinska Institutet (KI), Huddinge, Stockholm, Sweden
- 3 Karolinska Institutet (KI), Solna, Stockholm, Sweden
- 4 Umeå University, Umeå, Västerbotten, Sweden
- 5 Department of Medicine, Huddinge, Karolinska Institutet (KI), Huddinge, Stockholm, Sweden
- 6 University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
Tumor-residing microbiota poses a new challenge in cancer progression and therapy; however, the functional behavior of patient tumor-derived microbes remains poorly understood. We previously reported the presence of tumor microbiota in intraductal papillary mucinous neoplasms (IPMNs), which are precursors of pancreatic cancer. Here, we examined the metabolic and pathogenic potential of clinical microbiota strains obtained from IPMN tumors using various pancreatic cell lines and 3D spheroid models. Our findings revealed that several strains from IPMNs with invasive cancer or highgrade dysplasia, such as E. cloacae, E. faecalis, and K. pneumoniae, induced a cancer metabolite signature in human pancreatic cells when infected ex vivo. Bacterial invasiveness was significantly correlated with DNA damage in spheroids derived from normal and tumor-derived pancreatic cells, particularly in strains derived from advanced neoplasia IPMN and under hypoxic conditions.Additionally, microbial metabolites activate human mucosal-associated invariant T (MAIT) cells and restrict the infection, both extra-and intracellularly, in hypoxic tumor conditions and in synergy with antibiotics. Immune sensing of tumor microbiota metabolites may have clinical implications in cancer management.
Keywords: Pancreatic neoplasm, Tumor microbiota, Metabolites, spheroids, DNA Damage, MAIT cells, Immunotherapy
Received: 29 Dec 2024; Accepted: 19 Mar 2025.
Copyright: © 2025 Tajpara, Sobkowiak, Healy, NAUD, Gündel, Halimi, Ahmad Khan, Gabarrini, Le Guyader, Imreh, Haines, Del Chiaro, D'Alessandro, Heuchel, Löhr, Özenci and Sällberg Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Margaret Sällberg Chen, Department of Laboratory Medicine, Karolinska Institutet (KI), Solna, SE-171 77, Stockholm, Sweden
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