Dr Oliver M. Pearce
Group Leader
Overview
The focus of our research is the tumour microenvironment (TME). We are particularly interested in understanding the composition and function of the tumour extracellular matrix in immunosuppression.
Team
Daire Hanna
Clinical Research Fellow
Dr Celia Martin-Otal
Postdoctoral Researcher
Vinuja Premakumar
PhD Student
Marcos Burger Ramos
PhD Student
Ludovica Tarantola
PhD Student
Dr Tanith Westerman
Clinical Research Fellow
Research
What we do
We are investigating the composition and function of the tumour extracellular matrix, which has been identified as a barrier to immunotherapy response. Our overall goal is to target this barrier to improve patient response rates to immunotherapy. Towards this goal we are characterizing the tumour extracellular matrix and developing 3D tumour models for functional studies. The lab uses a combination of molecular biology, biochemistry, and genetic engineering approaches.
Our methods and technology
To study the tumour microenvironment, our lab has developed some methodology and technology that is unique to our lab.
Matrisome proteomics and glycomics. Up until quite recently it was difficult to characterise the tissue composition of tumour tissues. We use a matrisome proteomics approach to characterise the composition of tumour tissue at the translational (protein) level and the post-translational (glycan) level. We use these types of information to identify potential molecules within the tumour microenvironment that might play an active role in disease progression.
Engineered 3D tumour microenvironments. To test the role of our target molecules we use several 3D in vitro tumour models made from primary human cancer tissues. These provide a physiologically relevant and semi high throughput platform to exploring tumour progression, tumour immunity, and emerging biological therapies.
Bioinformatics. We use informatic approaches to analyze our characterization data sets. In particular we integrate protein and glycan data as a way to identify highly disease specific markers called ‘glycoforms’.
Current research projects:
- Research Project 1: The role of the tumour matrix on immune cell activation
In our previous studies, we have deconstructed the TME of high grade serous ovarian cancer (HGSC) and identified twenty-two ECM molecules that we use as a quantified ratio or ‘matrix index’, MI, found to be common in many human carcinomas (Pearce, Delaine-Smith, Maniati, et al. 2018). A major finding from this work has been the strong correlation of the MI with immunosuppressive immune cell phenotypes and poor prognosis in solid tumour patients. Understanding how the ECM disrupts anti-tumour immunity and regulates the local immune environment could identify new targets to treat many cancers. Our hypothesis is, components of the MI communicate with tumour infiltrating immune cells to generate immunosuppressive phenotypes. This work is being done by Elliott Puttock, in collaboration with Dr. Ann White at UCB Pharma.
- Research Project 2: Characterising the glycan shield of the tumour extracellular matrix
Complementary to project 1, the aim of this work is to further investigate the MI (described above) in triple negative breast cancer tissues, including characterising the post-translational modifications on MI proteins, which we think are important in generating the immunosuppressive TME. This work is being done by Ying Liu and Priyanka Hirani in my lab, and in collaboration with Dr. Alexandra Naba (University of Illinois, Chicago), Dr. Pedro Cutillas (QMUL), and Dr. Stuart Haslam (Imperial College London).
- Research Project 3: Investigating a specific Matrix Index molecule in forming an immune-barrier within the tumour microenvironment.
As a result of research project 2, we have identified one particular matrix index molecule that associates with inhibition of cytotoxic T-cell infiltration within the tumour microenvironment. Taking a biochemical approach we are following up on this observation to characterise the proteoglycans structure and immunological function. This work is being done by Priyanka Hirani in my lab, in collaboration with Dr. Pedro Cutillas (BCI), and Prof. Tom Wight (Benaroya Research Institute, Seattle).
Key Publications
Deconstructing a metastatic human tumor microenvironment. Cancer Disc (2018) 3, 304-319. PMID: 29196464
Characterization of the extracellular matrix of normal and diseased tissues using proteomics. J Proteome Res (2017) 16, 3083-3091. PMID: 28675934
A red meat-derived glycan promotes inflammation and cancer progression. PNAS (2015) 112, 542-547. PMID: 25548184
Engagement of myelomonocytic Siglecs by tumor-associated ligands regulates innate immune responses to cancer. PNAS (2014) 111, 14211-14216. PMID: 25225409
See recent publicationsMajor Funding
- 2019-2025- Cancer Research UK, ‘Restoring response to immunotherapy by targeting the extracellular matrix’,’ £813,040
- 2018-2019- Against Breast Cancer, Characterising the glycan shield of the extracellular matrix
Biography
I originally trained as an organic chemist with Prof Ben Davis and Prof Len Seymour at Oxford University. My PhD thesis was on the development of chemically glycosylated viral vectors for cancer gene therapy.
For my post-doctoral studies I moved to Prof. Ajit Varki’s lab at the University of California, San Diego. Here I investigated how glycans are involved in cancer immunity. After five years in California, I returned to the UK for a second post-doc with Prof. Fran Balkwill at Barts Cancer Institute to further train in cancer biology.
In September 2017 I started my own research program with funding from UCB Pharma and Against Breast Cancer. The theme of our work is the tumour matrisome and its role in tumour immunity.
Related News
‘Sugar-coated’ tumour matrix may offer way to make triple-negative breast cancer easier to treat
Researchers at Barts Cancer Institute, Queen Mary University of London, have discovered a way in which the environment surrounding triple-negative breast cancer cells helps suppress our immune system, making this cancer harder to treat. The findings open the door to a potential new treatment strategy that could make triple-negative breast cancers more vulnerable to the immune system and help more people to benefit from immunotherapy in future.
Publications 18 June 2026
Scientists uncover protein with the power to help or hinder breast cancer progression
The findings could help more patients to benefit from the latest advances in immunotherapies.
General News 30 April 2024
Ovarian cancer’s protective barrier: how the tumour matrix teaches cells to disarm immune attack
The results suggest new strategies to overcome the cancer’s defences and treat patients more effectively
General News 15 May 2023
Building a human tumour microenvironment in the lab
Researchers from Barts Cancer Institute at Queen Mary University of London, led by Professor Fran Balkwill and Dr Oliver Pearce, have built two 3D multi-cellular models of the human tumour microenvironment (TME) in ovarian cancer. The models, which are the first created from the CanBuild project, have revealed novel insights into the role of the TME in cancer progression.
General News 15 June 2021
CRUK Career Establishment Award
Dr Oliver Pearce has received a Cancer Research UK Career Establishment Award, which will fund a project that will look at restoring response to immunotherapy in triple-negative breast cancer.
General News 4 July 2019