Research

Understanding the Immune Regulation of Metastasis

Why do tumours metastasise to certain organs and not others? Why do only a small fraction of disseminated tumour cells succeed in forming overt metastases, while the majority fail? What barriers must these cells overcome, and through which mechanisms?

These are fundamental and long-standing questions in cancer research. Despite extensive investigation, our understanding of metastasis, particularly the early events leading to successful colonisation, remains limited. A key challenge has been the lack of tools to visualise and dissect these processes in vivo.

We are now entering a period of rapid technological advancement, offering unprecedented opportunities to explore the cellular and molecular dynamics of cancer progression. Over the past decade, several novel tools have been developed, including Cherry-niche, an innovative in vivo labelling system I created to allow cancer cells to mark and identify their neighbouring cells within the metastatic microenvironment (Ombrato et al., Nature 2019, Ombrato et al., Nature Protocols 2021, Ombrato, Nature Reviews Cancer 2022).

My lab focuses on decoding how immune cells regulate metastasis, with particular emphasis on innate immunity. We aim to define the cellular interactions that enable disseminated tumour cells to create a permissive metastatic niche and escape immune surveillance. Our ultimate goal is to inform new therapeutic strategies to prevent or disrupt metastasis.

Current research topics include:

• Investigating how the immune niche evolves during metastasis progression and how cross-talk between distinct myeloid populations drives this process.
• Exploring the local and systemic effects of radiotherapy on the tumour immune microenvironment during metastatic colonisation.
• Uncovering how myeloid cells suppress lymphocyte cytotoxicity, enabling metastatic tumour outgrowth.

Other Activities

• Member of the British Association for Cancer Research
• Member of the European Association for Cancer Research

Major Funding

• 2024-2030 – CRUK Career Establishment Award, “Controlling metastasis formation through inhibition of myeloid cell-myeloid cell cross-talk”, £ 744,16
• 2022-2025 - The Academy of Medical Sciences, Springboard Award, “Characterising neutrophil:macrophage cross-talk in metastatic niches”, £99,997
• 2022-2023 - Bowel Research UK, Inaugural Grant Award, Identify new strategies to prevent immune cells supporting liver metastasis in colorectal cancer, £50,000
• 2020-2022 - Barts Charity, Studying tumour microenvironment in metastasis.

Recent Publications

Isolation of Live Immune Cells from the Tumor Microenvironment by FACS Kafka A, Ermogenous C, Ombrato L (2024) 2748(10) 1-12

In vivo labelling system to study cell neighbourhoods Ombrato L Nature Reviews Cancer (2022) 22(10) 661-661

Early functional mismatch between breast cancer cells and their tumour microenvironment suppresses long term growth Perdrix Rosell A, Maiques O, Martin JAJ et al. Cancer Letters (2022) 544(10) 215800

Disrupted control of origin activation compromises genome integrity upon destabilization of Polε and dysfunction of the TRP53-CDKN1A/P21 axis Borel V, Boeing S, Van Wietmarschen N et al. Cell Reports (2022) 39(10) 110871

Author Correction: Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization Nolan E, Bridgeman VL, Ombrato L et al. Nature Cancer (2022) 3(10) 519-519

Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization Nolan E, Bridgeman VL, Ombrato L et al. Nature Cancer (2022) 3(10) 173-187

Early functional mismatch between breast cancer cells and their tumour microenvironment suppresses long term growth Rosell AP, Maiques O, Chakravarty P et al. (10) 2021.06.15.448466

Integrated OMICs unveil the bone-marrow microenvironment in human leukemia Passaro D, Garcia-Albornoz M, Diana G et al. Cell Reports (2021) 35(10) 109119

Generation of neighbor-labeling cells to study intercellular interactions in vivo Ombrato L, Nolan E, Passaro D et al. Nature Protocols (2021) 16(10) 872-892

Technical Advancements for Studying Immune Regulation of Disseminated Dormant Cancer Cells Ombrato L, Montagner M Frontiers in Oncology (2020) 10(1) 594514-594514

Team

• Marti Brucoli

• Christos Ermogenous
• Alessandra Perini

Biography

I completed my PhD in the lab of Prof. Maria Pia Cosma, first at the Telethon Institute for Genetics and Medicine (TIGEM, Naples, Italy) and then at the Centre for Genomic Regulation (CRG, Barcelona, Spain), where I used the induced pluripotent stem cell (iPSc) technology to study the molecular mechanisms of somatic cell reprogramming. Our work was among the first to highlight the role of epigenetic changes in this process.

For my post-doctoral research, I joined Dr Ilaria Malanchi’s lab at The Francis Crick Institute (London, UK), where I developed Cherry-niche, an in vivo labelling tool to study how the tumour microenvironment supports metastatic growth. This approach led to the discovery of parenchymal tissue cells as a previously unrecognised component of the metastatic niche.

In 2020, I established my own group at the Barts Cancer Institute, Queen Mary University of London. The theme of our work focuses on the role of immune cell interactions in metastasis formation.