Pre-Cancer Immunology

Group leader

Dr James Reading

UKRI Future Leaders Fellow
CRUK Lung Cancer Centre of Excellence

PhD and Postdoc positions available. Please enquire via email.

• Email: j.reading@ucl.ac.uk
• LinkedIn: James Reading
• X: jl_reading

UCL Profile

Our vision to intercept cancer

Our team believes that the immune system can be weaponised to detect and intercept the development of invasive tumours. We are exploring this idea by addressing three questions:

1. How do T cells engage with developing neoplasia during carcinogenesis?
2. Can we exploit signals of early T cell engagement to track underlying tumour development?
3. What are the defects in the nascent T cell response that we could target to intercept progression of pre-cancerous lesions?

Our ambition is to develop T cell focused blood tests and precision immune-interception drugs that can track and target carcinogenesis, respectively.

Our research: T cell-directed interception of lung cancer

Lung Cancer is the largest cause of cancer mortality worldwide due in part to late-stage presentation and treatment, underscoring an urgent need for new early detection and prevention technologies. Work in pre-clinical models suggests that T cells recognise neoantigens during carcinogenesis, leading to an incipient phase of T cell dysfunction. Several groups have found corresponding evidence of early immune regulation during preinvasive disease in human bronchial biopsies. However, the precise cellular and molecular events that govern this process are undefined. Delineating how the T cell network is regulated and restructured during pulmonary carcinogenesis may unlock methods to track and target lung tumour development. 

To tackle this challenge, we are mapping preinvasive T cell recognition, recirculation and regulation in individuals who develop lung cancer during chest computerised tomography (CT) and autofluorescent bronchoscopy surveillance. By applying cross-tissue, antigen-specific multi-omic T cell profiling in samples from individuals developing lung cancer we can precisely define detectable and targetable elements of T cell remodelling during the initial phase of anti-tumour immunity. This data is helping us to define when and how to intercept immune regulatory pathways that foster lung cancer development. 

To complement our work in clinical samples we use carefully calibrated autochthonous pre-clinical mouse models, allowing us to test new lung cancer interception regimens and gain deeper mechanistic insight into the immune-regulatory pathways that drive preinvasive pulmonary disease progression. By generating an integrated, T cell-centric framework to track and target development of invasive tumours we hope to identify and prophylactically treat individuals with progressive preinvasive lesions or nodules, so that we can prevent lung cancer. It is possible that a fraction of these pathways will be active in other pre-cancers, allowing us to charter a roadmap for multi-cancer interception.  

Our story

The Pre-Cancer Immunology lab was initiated with a UCLH BRC NIHR Fellowship in 2021, before officially launching with funding from a UKRI Future Leaders Fellowship started in June 2022. Since then, we have expanded into a multidisciplinary, vibrant and dynamic team of 13 wet and dry lab basic and clinical researchers undertaking PhDs or Postdoctoral training in Pre-Cancer Immunology. We work across three inter-connected cores:

1. The T cell Reactivity core, who are profiling epitope specificity of T cells in preinvasive lesions
2. The Interception core, who map and target T cell regulation in progressive pre-malignant lesions/nodules
3. The Early detection core who are using T cell omics to detect underlying progressive preinvasive disease and identify individuals at risk of cancer.

Research Team

Selected Publications

Funding