The Impact of Obesity on Immune Modulation in Breast Cancer Metastasis and Immunotherapy Outcomes

Lead Principal Investigator: Dr Charles Birts

Co-investigators: Professor Stephen Beers, Professor Max Crispin

Research Technician: Anna Liese-Silber

Location: University of Southampton

Dates:  October 2025 – September 2028     Status: In Progress

Funding: £243,000

Research Theme: Therapies, Prevention

Aims

The Fellowship project is investigating how obesity influences breast cancer progression, particularly cancer spread and treatment response. Breast cancer is one of the most common cancers worldwide, and obesity is associated with increased metastasis and poorer treatment outcomes. Previous work in Dr Birts’ laboratory has shown that excess body fat alters immune cell function within the tumour environment, reducing the body’s ability to fight cancer.

Based at the University of Southampton’s Centre for Cancer Immunology, the team are studying how early breast tumours may send signals that prepare distant organs, such as the lungs and bones, for cancer spread. In particular, neutrophils, a type of immune cell, may help create conditions that favour metastasis in obesity.

Researchers will be using a newly developed 3D ‘mini-tumour’ research model that includes human breast cancer cells, fat cells, immune cells, and supporting tissue. It’s the laboratory system to closely replicate the inflamed, fatty tumour environment found in obesity. The findings were published in the Nature npj Breast Cancer Journal in 2025.

The Fellowship also aims to improve treatment effectiveness. The team will investigate whether metformin, a widely used diabetes drug, can enhance anti-tumour immune responses and improve the efficacy of immunotherapies. In addition, other metabolic therapies, including GLP-1 agonists, also known as weight-loss jabs (e.g. Ozempic), will be tested for their ability to reduce tumour growth and boost the effectiveness of immunotherapy treatments. The part of the work investigating the effect of weight-loss drugs on breast cancer was recently covered by ITV News featuring comments by Dr Charlie Birts, Dr Mark Powell, ABC’s Head of Research, and Professor Simon Lord, ABC Oriel College, Senior Research Fellow.

Anna-Liese Silber, Technician working on the Dr Charlie Birts ABC Fellowship

Overall, this research seeks to identify new approaches to prevent breast cancer spread and improve treatment outcomes, particularly for patients with obesity, by better understanding the links between metabolism, immunity and cancer.

Against Breast Cancer’s mission is to fund research that prevents loss of life from secondary breast cancer, the leading cause of breast cancer deaths. This new Fellowship led by Dr Birts, complements our existing ABC Discover and ABC Therapeutic Antibody programmes, which are funded for five and ten years, respectively.

Publications

Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2 + breast carcinoma Birts CN, Savva C, Laversin SA, Lefas A, Krishnan J, Schapira A, Ashton-Key M, Crispin M, Johnson PWM, Blaydes JP, Copson E, Cutress RI, Beers SA. Sci Rep. 2022 May 24;12(1):7802.

Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing Blyth RRR, Laversin SA, Foxall RB, Savva C, Copson E, Cutress RI, Birts CN, Beers SA. NPJ Breast Cancer. 2025 May 30;11(1):50

The role of three-dimensional in vitro models in modelling the inflammatory microenvironment associated with obesity in breast cancer. Blyth RRR, Birts CN, Beers SA. Breast Cancer Res. 2023 Sep 11;25(1):104