Pre-Cancer Immunology Laboratory

The Reading lab are mapping pre-invasive T cell dynamics during carcinogenesis to detect and intercept cancer development.

Group Leader:听Dr James Reading

Our Vision for Cancer Interception听

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

How do T cells engage with developing neoplasia during carcinogenesis?
Can we exploit signals of early T cell engagement to track underlying tumour development?
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.听

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.听

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.听听

Our Story

The Pre-Cancer Immunology lab was initiated with a 果冻影院H 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听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: i) The T cell Reactivity core, who are profiling epitope specificity of T cells in preinvasive lesions, ii) The Interception core, who map and target T cell regulation in progressive pre-malignant lesions/nodules and the iii) 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. Reading, J. L., Caswell, D. R., Swanton, C. Nature Genetics (2023) Sept 27; 55, 1610-1612. DOI: 10.1038/s41588-023-01492-x

2. Hwant, E. S., Reading, J., Yu, J., Paolo Dotto, G., Grady, W. M., Czerniak, B., Serrano, M. Cancer Cell. (2023) Apr 10; 41 (4): 637-640. Doi: 10.1016/j.ccell.2023.03.012

3.. Reading, J. L., Foster, K., Joshi, K., Chain, B.听Cancer Cell. (2022) Apr 11; 40 (4): 351 - 353. Doi: 10.1016/j.ccell.2022.03.007听

4.听. Kevin Litchfield*,听James L Reading*, Clare Puttick*, Krupa Thakkar, Chris Abbosh, Robert Bentham, Thomas B. K. Watkins, Rachel Rosenthal, Dhruva Biswas, Andrew Rowan, Emilia Lim, Maise Al Bakir, Virginia Turati, Jos茅 Afonso Guerra-Assun莽茫o, Lucia Conde, Andrew J.S. Furness, Sunil Kumar Saini, Sine R Hadrup, Javier Herrero, Se-Hoon Lee, Peter Van Loo, Tariq Enver, James Larkin, Matthew D. Hellmann, Samra Turajlic, Sergio Quezada, Nicholas McGranahan, Charles Swanton.
Cell. (2021) Feb 4;184(3):596-614.e14. doi:听10.1016/j.cell.2021.01.002.

5.听 Reading, J. L#., Roobrouck, V. D., Hull, C. M., Becker, P. D., Beyens, J., Valentin-Torres, A.,听听Boardman, D., Lamperti, E. N., Stubblefield, S., Lombardi, G., Deans, R., Ting, A. E., Tree, T. Front. Immunol. (2021) Sept 1. Doi: 10.3389/fimmu.2021.716606

6.听. Kevin Litchfield*, James L. Reading*, Emilia L. Lim, Hang Xu, Po Liu, Maise Al-Bakir, Yien Ning Sophia Wong, Andrew Rowan, Samuel A. Funt, Taha Merghoub, David Perkins, Martin Lauss, Inge Marie Svane, G枚ran J枚nsson, Javier Herrero, James Larkin, Sergio A. Quezada, Matthew D. Hellmann, Samra Turajlic & Charles Swanton*.听Nat Commun., (2020). July 听11 (1), 3800. Doi:10.1038/s41467-020-17526-5
*equal contribution

7.听. Ghorani, E*, Reading, J. L.*#, Henry, J. Y., Massy, M. R. D., Rosenthal, R., Turati, V., Joshi, K., Furness, A., Ben Aissa, A., Kumar Saini, S. et alRamskov S, Georgiou A, Sunderland MW, Wong YNS, De Mucha MV, Day W, Galvez-Cancino F, Becker PD, Uddin I, Ismail M, Ronel T, Woolston A, Jamal-Hanjani M, Veeriah S, Birkbak NJ, Wilson GA, Litchfield K, Conde L, Guerra-Assun莽茫o JA, Blighe K, Biswas D, Salgado R, Lund T, Al Bakir M, Moore DA, Hiley CT, Loi S, Sun Y, Yuan Y, AbdulJabbar K, Turajilic S, Herrero J, Enver T, Hadrup SR, Hackshaw A, Peggs KS, McGranahan N, Chain B, Swanton C , Quezada SA.听Nature Cancer (2020) May 1 (5), 546-561. Doi: 10.1038/s43018-020-0066-y
*equal contribution
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Nature Community Behind the Paper:听听(video)
Nature Community Behind the Paper:听

8. 听Joshi K*, Robert de Massy M*, Ismail M*, Reading JL, Uddin I, Woolston A, Hatipoglu E, Oakes T, Rosenthal R, Peacock T, Ronel T, Noursadeghi M, Turati V, Furness AJS, Georgiou A, Wong YNS, Ben Aissa A, Werner Sunderland M, Jamal-Hanjani M, Veeriah S, Birkbak NJ, Wilson GA, Hiley CT, Ghorani E, Guerra-Assun莽茫o JA, Herrero J, Enver T, Hadrup SR, Hackshaw A, Peggs KS, McGranahan N, Swanton C, Quezada SA, Chain B. Nat Med. (2019) Oct;25(10):1549-1559. Doi: 10.1038/s41591-019-0592-2

9.听. Rosenthal R, Cadieux EL*, Salgado R*, Bakir MA*,听Moore DA*, Hiley CT*, Lund T*, Tani膰 M, Reading JL, Joshi K, Henry JY, Ghorani E, Wilson GA, Birkbak NJ, Jamal-Hanjani M, Veeriah S, Szallasi Z, Loi S, Hellmann MD, Feber A, Chain B, Herrero J, Quezada SA, Demeulemeester J, Van Loo P, Beck S, McGranahan N, Swanton C. Nature. (2019) March; Doi: 10.1038/s41586-019-1032-7

10.听. Wong YNS, Joshi K, Khetrapal P, Ismail M, Reading JL, Sunderland MW, Georgiou A, Furness AJS, Ben Aissa A, Ghorani E, Oakes T, Uddin I, Tan WS, Feber A, McGovern U, Swanton C, Freeman A, Marafioti T, Briggs TP, Kelly JD, Powles T, Peggs KS, Chain BM, Linch MD, Quezada S. J Exp Med. (2018) Nov 5;215(11):2748-2759. Doi: 10.1084/jem.20181003

11.听 Reading, J. L*#, G谩lvez-Cancino, F*., Swanton, R. C., Lladser, A., Peggs, K., & Quezada, S. Immunological Reviews (2018) May;283(1):194-212. Doi: 10.1111/imr.12657

12.听. Turajlic S*, Litchfield K*, Xu H, Rosenthal R, McGranahan N, Reading JL, Wong YNS, Rowan A, Kanu N, Al Bakir M, Chambers T, Salgado R, Savas P, Loi S, Birkbak NJ, Sansregret L, Gore M, Larkin J, Quezada SA, Swanton C. Lancet Oncol. (2017) Aug;18(8):1009-1021. Doi: 10.1016/S1470-2045(17)30516-8

13.听. Reading, J. L., & Quezada, S. A. (2016). Immunity, 45 (6), 1181-1183. Doi: 10.1016/j.immuni.鈥�2016.12.004