logo white

Advancing treatments

Research Menu

Modulating the gut microbiome to improve immunotherapy outcomes in mesothelioma.

Pleural mesothelioma is aggressive and currently, incurable.  The immunotherapy combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) has been a groundbreaking treatment for mesothelioma and has significantly improved outcomes for some patients.  However, treatment efficacy can vary widely among individuals and is poorly understood.

This project aims to investigate the role of the gut microbiome in modulating response to first-line immunotherapy in mesothelioma. In parallel, it will evaluate the efficacy of faecal microbiota transplantation (FMT) as a novel, non-invasive strategy to enhance immunotherapy effectiveness.

What we will do

Led by senior medical oncologist A/Prof Anthony Linton, this study will recruit a minimum of 50 patients with mesothelioma who are commencing first-line immunotherapy through hospitals in Australia. Stool samples and matched peripheral blood samples will be collected at baseline, week 4, and week 12 after treatment initiation, with additional follow-up sampling at disease progression where feasible.
Metagenomic sequencing of stool samples and flow cytometric profiling of peripheral blood mononuclear cells (PBMCs) will be performed and correlated with clinical outcomes to identify microbiome–immune signatures associated with treatment response. FMT will be evaluated in preclinical animal models to explore its therapeutic efficacy and mechanistic impact on immunotherapy response.

Importance

Mesothelioma is an aggressive and incurable cancer with limited treatment options. While the introduction of immunotherapy has significantly improved outcomes for a subset of patients, the majority derive limited benefit. Understanding and harnessing the gut microbiome’s role in shaping immunotherapy responsiveness has the potential to extend clinical benefit to a much larger proportion of patients.

Anticipated outcomes

This project is expected to identify key microbial and immune signatures associated with immunotherapy response and resistance, and to establish FMT as a promising adjuvant strategy to enhance treatment efficacy.

Benefits

The study will provide foundational evidence to support microbiome-based interventions in mesothelioma and pave the way for future clinical trials incorporating FMT to improve survival and treatment outcomes for patients.

Funding support

This project is funded by a Discovery and Innovation Grant ($294,250; 2026–2029) from the NSW Dust Diseases Board, administered through iCare NSW.

This project would not be possible without the funding support of Trevor and Shirley Seaman. Trevor is a mesothelioma patient and is a tireless advocate for research to improve survival outcomes.  Read Trevor’s story here.

About the researcher…

Peter Shi

Dr Peter (Huaikai) Shi

Post-Doc Fellow

Dr Shi joined ADDRI after being awarded a PhD in Jan 2021, where he can utilise his expertise in immunology and animal modelling in thoracic cancer research. Dr Shi established preclinical cell and animal models to develop a novel approach that combines beneficial immunotherapy with anti-cancer natural products to improve the treatment outcome of the current incurable cancer malignant mesothelioma. His work is now translated into a Phase 1 clinical trial to investigate Leptospermum extract (QV0) as a novel anti-drug for mesothelioma. If successful, this will provide a natural option for combinational treatment in pleural mesothelioma. In the meantime, Dr Shi discovered that tumour cells grown in a 3D dimension produced a hypoxic core that led to alterations in gene and microRNA expression. Dr. Shi has published in prestigious peer-reviewed papers that testify his contributions to the field of thoracic cancer research where he designed and carried out experiments, analysed the data and wrote manuscripts. His current research interests investigate the microbiome in mesothelioma and its links to the efficacy of immunotherapy.

linkedin

Grants

Publications

publications icon Fermented rice bran extract delays skin aging by increasing the synthesis of collagen and elastin.
publications icon Androgen deprivation promotes diabetic wound healing in mice through modulation of wound microbiome and immune response.
publications icon A combination of PD-1 and TIGIT immune checkpoint inhibitors elicits a strong anti-tumour response in mesothelioma.
publications icon Unlocking the role of wound microbiome in diabetic, burn, and germ-free wound repair treated by natural and synthetic scaffolds.
publications icon Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis
publications icon The contradictory role of androgens in cutaneous and major burn wound healing
publications icon Exploring MicroRNA and exosome involvement in malignant pleural mesothelioma drug response
publications icon Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone (PCL) electrospun scaffold accelerates burn wound healing
publications icon Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics
publications icon Advanced pathophysiology mimicking lung models for accelerated drug discovery
publications icon 3-Dimensional mesothelioma spheroids provide closer to natural pathphysiological tumour microenvironment for drug response studies

Our Research Projects

We conduct biomedical (preclinical), clinical and public health research into asbestos-related diseases with findings enabling improved methods of prevention, diagnostic, therapeutic procedures, and treatments.

Read more

Sign up to our newsletter

Sign up
Skip to content