Pre-Cancer Immunology

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

1. Clonal driver neoantigen loss under EGFR TKI and immune selection pressures. Al Bakir M, Reading JL, Gamble S, Rosenthal R, Uddin I, Rowan A, et al. Nature. 2025 Feb 19.
2. Beta papillomaviruses: From foe to friend in skin cancer immunity. Lebrusant-Fernandez M, Reading JL. Cancer Cell. 2025 Jan 13;43(1): 6-7. doi: 10.1016/j.ccell.2024.12.005.
3. Tumor heterogeneity impairs immunogenicity in mismatch repair deficient tumors. Reading JL, Caswell DR, Swanton C. Nature Genetics (2023) Sept 27; 55, 1610-1612.
4. Pre-Cancer: From diagnosis to intervention opportunities. Hwant ES, Reading JL, Yu J, Paolo Dotto G, Grady WM, Czerniak B, Serrano M. Cancer Cell. (2023) Apr 10; 41 (4): 637-640.
5. Tracking down tumor-specific T cells. Reading JL, Foster K, Joshi K, Chain B. Cancer Cell. (2022) Apr 11; 40 (4): 351-353.
6. Meta-analysis of Tumour and T cell intrinsic mechanisms of sensitization to checkpoint inhibition. Litchfield K*, Reading JL*, Puttick C*, Thakkar K, Abbosh C, Bentham R, et al. Cell. (2021) Feb 4;184(3): 596-614.e14.
7. Augmented Expansion of Treg Cells From Healthy and Autoimmune Subjects via Adult Progenitor Cell Co-Culture. Reading JL, Roobrouck, VD, Hull CM, Becker PD, Beyens J, et al. Front Immunol. 2021 Sep 1;12: 716606.
8. Escape from nonsense-mediated decay associates with anti-tumor immunogenicity. Litchfield K*, Reading JL*, Lim EL, Hang Xu, Po Liu, Al-Bakir-M, et al. Nat Commun. 2020 Jul 30;11(1): 3800.
9. The T cell differentiation landscape is shaped by tumour mutations in lung cancer. Ghorani E*, Reading JL*, Henry JY, Massy MRD, Rosenthal R, et al. Nature Cancer (2020) May 1 (5), 546-561. *equal contribution

• Nature Community Behind the Paper: Tumour neoantigens fuel CD4 and CD8 T cell exhaustion in lung cancer. (video)
• Nature Community Behind the Paper: Coupling T cell differentiation to the lung cancer mutanome via neoantigen surveillance

10. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer. Joshi K*, Robert de Massy M*, Ismail M*, Reading JL, Uddin I, Woolston A, et al. Nat Med. (2019) Oct;25(10): 1549-1559.
11. Neoantigen-directed immune escape in lung cancer evolution. Rosenthal R, Cadieux EL*, Salgado R*, Bakir MA*, Moore DA*, Hiley CT*, Lund T*, Tanić M, Reading JL, et al. Nature. (2019) March.
12. Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment. Wong YNS, Joshi K, Khetrapal P, Ismail M, Reading JL, Sunderland MW, et al. J Exp Med. (2018) Nov 5;215(11): 2748-2759.
13. The function and dysfunction of memory CD8+ T cells in tumor immunity. Reading JL*, Gálvez-Cancino F*, Swanton RC, Lladser A, Peggs K & Quezada S. Immunological Reviews (2018) May;283(1): 194-212.
14. Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. Turajlic S*, Litchfield K*, Xu H, Rosenthal R, McGranahan N, Reading JL, Wong YNS, et al. Lancet Oncol. (2017) Aug;18(8): 1009-1021.
15. Too Much of a Good Thing? Chronic IFN Fuels Resistance to Cancer Immunotherapy. Reading, JL & Quezada SA (2016). Immunity, 45 (6), 1181-1183.