A conversation with Fadi Issa about his recent article on regulatory T cell therapy in kidney transplants. In this episode of To Immunity and Beyond, Paul Klenerman talks with surgeon and immunologist Fadi Issa about pioneering regulatory T-cell therapy in kidney transplantation. Fadi shares his journey from reconstructive surgery to immune tolerance research and discusses the groundbreaking, first-in-human ONE Trial of T reg therapy in kidney transplantation. The trial showed promising graft survival rates, and found B cell-enriched focal lymphocytic infiltrates in the T reg treated group. Paul and Fadi also explore how current work with spatial transcriptomics will enable further insights into this mechanism. Full article: Oliver McCallion, Amy R. Cross, Matthew O. Brook, Conor Hennessy, Ricardo Ferreira, Dominik Trzupek, William R. Mulley, Sandeep Kumar, Maria Soares, Ian S. Roberts, Peter J. Friend, Giovanna Lombardi, Kathryn J. Wood, Paul N. Harden, Joanna Hester, Fadi Issa, Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants, Med, Volume 6, Issue 5, 2025, 100561, ISSN 2666-6340, https://doi.org/10.1016/j.medj.2024.11.014.

A conversation with Miles Carroll and Oliver Meek about their recent Ebola virus persistence review article. In this episode, Oliver Meek and Miles Carroll discuss their recent review on Ebola virus (EBOV) persistence, set against the broader context of the West African epidemic. They share insights into how viral reservoirs form in immune-privileged sites and the immunological signatures linked to resistance. The conversation explores the implications of these findings on sexual transmission of EBOV, therapeutic development and strategies to prevent viral persistence and recrudescence. They also consider how these mechanisms may inform approaches to other emerging infectious diseases. Full article: Meek O, Fornace K, Carroll MW. Ebola virus persistence: implications for human-to-human transmission and new outbreaks. Explor Med. 2025;6:1001333. https://doi.org/10.37349/emed.2025.1001333 Further reading: Züst R, et al. Presence and Persistence of Andes Virus RNA in Human Semen. Viruses. 2023 Nov 17;15(11):2266. https://doi.org/10.3390/v15112266

A conversation with Zakiya Leeming and Rachel Hindmarsh about the Thanks for the Memories project and a new opera. The Thanks for the Memories public engagement programme is about to premier a new opera, ‘Dangerous Matter’, at the Royal Northern College of Music on June 24th, 2025, inspired both by the story of Lady Mary Wortley Montagu, and by research into immune memory. On this episode we talk to composer Zakiya Leeming and facilitator Rachel Hindmarsh about how they developed the opera, and find out about their wider creative programme of science and music engagement with secondary school students. The project would like to thank the Wellcome Trust, who have supported the project through an Enriching Engagement Grant. The project would also like to thank researchers at the University of Oxford and University of Manchester who have supported scientific engagement throughout the project. Further reading: · Project website: https://www.immunology.ox.ac.uk/about/public-engagement/thanks-for-the-memories-t4tm · Zakiya Leeming article on the process of writing the opera: https://oxfordroadcorridor.com/medicine-memory-and-the-music-of-defiance/ · Dawn, on the Morning after the Storm - collaboration between Zakiya and the International Severe and Acute Respiratory and Emerging Infection Consortium (ISARIC) during Covid pandemic https://www.youtube.com/watch?v=e0l3S04TfFY; Guardian article about the performance https://www.theguardian.com/music/2021/jun/16/musical-composition-inspired-by-uk-covid-research-to-have-world-premiere · PRISM website https://www.rncm.ac.uk/research/research-activity/research-centres-rncm/prism/

A conversation with Ben Fairfax about the recent article: CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade. This episode discusses Milotay, G., Little, M., Watson, R.A. et al. CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade. Nat Med (2025). https://doi.org/10.1038/s41591-025-03647-1. Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/

A conversation with Yang Hu about his recent article: Self-interactive learning: Fusion and evolution of multi-scale histomorphology features for molecular traits prediction in computational pathology. This episode discusses Yang Hu et al, ‘Self-interactive learning: Fusion and evolution of multi-scale histomorphology features for molecular traits prediction in computational pathology’, Medical Image Analysis, 101 (2025) https://doi.org/10.1016/j.media.2024.103437 The relevant study was supported by the PathLAKE Centre of Excellence for digital pathology and artificial intelligence which is funded by the Data to Early Diagnosis and Precision Medicine strand of the HM Government’s Industrial Strategy Challenge Fund, managed and delivered by Innovate UK on behalf of UK Research and Innovation (UKRI) (Grant ref: 104689/application number 18181), as well as NIHR Oxford Biomedical Research Centre. Views expressed are not necessarily those of the PathLAKE Consortium members, the NHS, the UKRI, the NIHR, Innovate UK or the Department of Health. The speaker would also like to thank the support from the Quantitative Bio-Image Group, led by Professor Jens Rittscher. Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/

Research on human cells in space may uncover the hidden mechanisms behind ageing. Exciting developments are underway at the Space Innovation Lab at the University of Oxford! The launch of human tissue samples to the International Space Station marks a bold and forward-looking step in scientific discovery—one aimed at unravelling the mysteries of ageing. This pioneering research holds tremendous potential for unlocking transformative insights into musculoskeletal health and regenerative medicine, paving the way for future breakthroughs that could benefit millions on Earth. Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/

Dr Kirsty McHugh and Dr Carolyn Nielsen discuss a recent Cell article: ‘Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype’. This episode discusses the following article: Barrett, J et al., Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype. Cell 187 (5 September 2024). https://doi.org/10.1016/j.cell.2024.06.015 Article funding and acknowledgments: https://www.sciencedirect.com/science/article/pii/S009286742400655X?via%3Dihub#ack0010 The paper discussed in this episode is the product of six years of work with important contributions made by many members of Prof Simon Draper’s blood-stage malaria team, as well as key external collaborators. Dr McHugh and Dr Nielsen would like to thank all authors for their input, in particular Jordan Barrett as first author, Dimitra Pipini for antibody expression, Giacomo Gorini as the early phase project lead, Nathan Wright for the structural work, and Brandon Wilder for the mouse model. USAID was the major funder. Full author list: Jordan R Barrett, Dimitra Pipini, Nathan D Wright, Andrew J R Cooper, Giacomo Gorini, Doris Quinkert, Amelia M Lias, Hannah Davies, Cassandra A Rigby, Maya Aleshnick, Barnabas G Williams, William J Bradshaw, Neil G Paterson, Thomas Martinson, Payton Kirtley, Luc Picard, Christine D Wiggins, Francesca R Donnellan, Lloyd D W King, Lawrence T Wang, Jonathan F Popplewell, Sarah E Silk, Jed de Ruiter Swain, Katherine Skinner, Vinayaka Kotraiah, Amy R Noe, Randall S MacGill, C Richter King, Ashley J Birkett, Lorraine A Soisson, Angela M Minassian, Douglas A Lauffenburger, Kazutoyo Miura, Carole A Long, Brandon K Wilder, Lizbé Koekemoer, Joshua Tan, Carolyn M Nielsen, Kirsty McHugh* and Simon J Draper*. *Joint senior authors. Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/

Dr. Barbara Kronsteiner-Dobramysl discusses a recent Metabolism article: ‘Starvation and infection: The role of sickness-associated anorexia in metabolic adaptation during acute infection’. This episode discusses the following article: Jindal, J, Hill, J, Harte, J, Dunachie, S, and Barbara Kronsteiner, B, Starvation and infection: The role of sickness-associated anorexia in metabolic adaptation during acute infection. Metabolism 161 (December 2024). https://doi.org/10.1016/j.metabol.2024.156035 Barbara would like to specifically thank Ms. Jessy Jindal for the initial idea for this review. As part of her medical studies at the University of Oxford she wrote an essay about starvation and infection which inspired this publication. This work matured over several years and was shaped by all the co-authors and valuable input from reviewers and the editor until it reached its final version that is published now. We hope it is of interest to many and sparks conversation and new ideas for studies in this area. Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/

Professor Omer Dusk discusses a bioRxiv pre-print: ‘Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes’. This episode discusses the following pre-print: 'Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes.' Burton J, Siller-Farfan JA, Andre V, Jenkins J, Barton MI, Bustamante Eguiguren S, Cabezas-Caballero J, Davis SJ, Weikl TR, van der Merwe PA, Dushek O (bioRxiv pre-print (2025), under review). https://www.biorxiv.org/content/10.1101/2025.01.06.631424v1 And references two related studies that provide foundational framework for the work: Using CombiCells, a platform enabling titration and combinatorial display of cell surface ligands, to study T cell antigen sensitivity by TCRs, CARs, and BiTEs Patel A, Andre V, Eguiguren SB, Barton MI, Denham EM, Pettmann J, Morch AM, Kutuzov MA, Siller-Farfan JA, Dustin ML, van der Merwe PA, Dushek O The EMBO Journal (2024) https://www.biorxiv.org/content/10.1101/2023.06.15.545075v2 Inefficient exploitation of accessory receptors reduces the sensitivity of chimeric antigen receptors Burton J, Siller-Farfan JA, Pettmann J, Salzer B, Kutuzov M, van der Merwe PA, Dushek O PNAS (2023). https://www.pnas.org/doi/abs/10.1073/pnas.2216352120 A full list of contributors and acknowledgements can be found within each article. Additionally, Professor Omer Dushek would like to thank past and present members of his laboratory, including all co-authors of the manuscript, and especially his long-term collaborator P. Anton van der Merwe (co-founder). The establishment of MatchBio Ltd relied on technology to improve the sensitivity of CAR-T cells and technology to manipulate surface proteins directly on the cell surface (CombiCells) that included critical contributions from Jake Burton, Jesús Siller-Farfan, Violaine Andre, Michael I. Barton, Ashna Patel, Eleanor Denham, Edward Jenkins, Simon J. Davis, Sofia Bustamante Eguiguren, Jose Cabezas Caballero, Thomas R Weikl, and Johannes Pettmann. The founding of MatchBio Ltd relied on the expertise of Philip G. Jakeman (CEO) and the OSE Life Science Panel. The work has been supported by the Wellcome Trust (207537/Z/17/Z) and UKRI MRC (MR/W031353/1). Speakers: Professor Omer Dushek, Professor Paul Klenerman Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/

Professor Quentin Sattentau discusses research published in 'Nature Communications' on the role of enzyme ADAM10 in mediating clearance of apoptotic T cells by macrophages. This episode discusses Drexhage, LZ, Zhang, S, Dupont, M, et al. Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis. Nat Commun. 15(1), 541 (2024). http://doi.org/10.1038/s41467-023-44619-8 Article funding and acknowledgments: https://www.nature.com/articles/s41467-023-44619-8#Ack1 Professor Sattentau thanks Linnea Drexhage and Shengpan Zhang (joint first authors) who worked really hard and provided most of the data, Niloofar Karaji who discovered the initial phenomenon, all the other authors for their excellent input, and the MRC for funding the project. Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/

Professor Astrid Iversen discusses research published in Nature, using historic genome data to investigate the emergence of genetic risk for multiple sclerosis in Northern Europe. This episode discusses Barrie, W, Yang, Y, Irving-Pease, EK, et al. Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations. Nature 625, 321–328 (2024). https://doi.org/10.1038/s41586-023-06618-z Article funding and acknowledgments: https://www.nature.com/articles/s41586-023-06618-z#Ack1 This study was international and multidisciplinary in nature, and Professor Iversen is grateful for the vital work done by Professor Willerslev, his group, and their collaborators. Professor Iversen also gratefully acknowledges the critical contributions of the shared first authors – William Barrie, Yaoling Yang, Evan K. Irving-Pease, Kathrine E. Attfield, Gabriele Scorrano, and Lise Torp Jensen – as well as those of fellow shared last authors: Daniel J. Lawson, Lars Fugger, and Eske Willerslev. Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/