‘CheckPAC’ intra-tumoural microbiota analysis (IRAS 357173)

Pancreatic and bile duct cancers are difficult to treat, and while immunotherapy can help some patients, we do not yet know why it works for some people and not others. We have found a strong link between a specific bacterium in stool samples and response to immunotherapy. We will examine tumour samples from patients who received immunotherapy to see whether this bacterium is present within the tumour and how it affects the body's immune response. Our findings could help us improve immunotherapy and develop new approaches to benefit patients with these hard-to-treat cancers.

Pancreatic and biliary tract cancers have a poor prognosis and limited treatment options. Although immunotherapy has shown benefit in some patients, there are currently no biomarkers that reliably predict treatment response. Analysis of acellular stool samples from patients enrolled in the CheckPAC phase II clinical trial (NCT02866383) identified a strong association between the presence of the bacterium Fusobacterium animalis and response to immunotherapy.

To investigate this finding further, we will analyse up to 145 tumour tissue samples collected from patients participating in the same ethically approved clinical trial. We will assess the presence of intra-tumoural bacteria, particularly Fusobacterium species, and characterise tumour immune signatures using genomic analyses, supported by imaging, histopathology staining, nucleic acid sequencing and, where appropriate, bacterial culture. The work seeks to determine whether tumour-associated bacteria influence anti-cancer immune responses and may help inform strategies to improve immunotherapy outcomes for patients with pancreatic and biliary tract cancers.

Rationale

Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) usually present insidiously, with the majority of cases detected at an advanced, unresectable stage and with average survival approximates of only 12 months with the current available treatments.

There is emerging evidence that the ‘gut microbiome’ may influence the efficacy of immune checkpoint inhibitor immunotherapy in solid organ tumours.

Examination of the gut microbiome (using stool DNA shotgun metagenomics) in participants of a phase 2 clinical trial looking at immunotherapeutic treatment in patients with pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) has shown that the is a strong association between the presence of the bacteria Fusobacterium animalis and poorer survival. There is evidence that the bacteria is able to move into gastrointestinal cancers, promoting inflammation and suppressing anti-tumour immunity.

Eventually, it is hoped this will lead to strategies to target intra-tumoural colonisation of bacteria to enhance ICI efficacy and improve outcomes for patients.

Aims

The study aims to:

• characterise the presence of intra-tumoural bacteria, particularly F. animalis, in tumour tissue samples of patients on the CheckPAC clinical trial (i.e. patients with advanced pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC)).

Primary Outcome

1. To identify the proportion of tumour samples with detectable intra-tumoural bacteria
2. To identify the proportion of tumour samples with detectable Fusobacterium animalis

Key Secondary outcome(s)

None

Study Type

Observational

Participant and Sample Information

Populations involved:

Participants on the CheckPAC clinical trial

Countries of recruitment:

International

Approximate participant or sample numbers (if applicable):

145

Key inclusion criteria:

Participants on the CheckPAC clinical trial

Key exclusion criteria:

Participants not on the CheckPAC clinical trial

Recruitment status:

Non-recruiting: Pre-collected samples only.

Governance and Ethical Approval

Governance and oversight:

Study Sponsor: Wellcome Sanger Institute

All work conducted at the Wellcome Sanger Institute is reviewed and overseen by institutional Research Governance processes, ensuring compliance with ethical, legal, and regulatory requirements.

Ethical approval:

This study has been reviewed by the East Midlands – Derby NHS Research Ethics Committee. The study received REC approval on 22 April 2025.

IRAS 357173

REC reference: 25/EM/0100

Data and Sample Use

Data sharing:

Anonymised DNA sequence data are stored in the European Genome-Phenome Archive (EGA) and made available to bonafide researchers via managed access, subject to data access agreements. Anonymised samples and cultured cells may also be shared with other legitimate research organisations under appropriate legal agreements.

IPD sharing statement

Deidentified individual participant-level data (IPD) will not be shared as part of this study.

Completion date 

Ongoing

Further Information

For enquiries about the scientific aims of this study or potential collaboration, please contact the relevant scientific programme at https://www.sanger.ac.uk/group/lawley-lab/.

For enquiries relating to research governance, ethics, or regulatory oversight, please contact the Research Governance team at researchgovernance@sanger.ac.uk.