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Peer-reviewedCC BYCell

Plasma signals of lung tumor promotion for molecular cancer prevention

  • Tej Pandya1
  • Maria Zagorulya2
  • Michelle M. Leung3
  • Marcellus Augustine4
  • Lydia Liu5
  • Aino‐Maija Leppä5
  • Ulysse Baruchel5
  • Sin Wi Ng6
  • Tamara Klockner2
  • Miriam Mugabo5
  • Anthony J. Griffen7
  • Oleg B. Blyuss8
75 more authors
  • Chrysante S. Iliakis9
  • Amalie Grenov10
  • Kerstin Haase11
  • David C. Muller12
  • K Chan13
  • Jincheng Wu14
  • Vernon A. Burk15
  • Neil Wright16
  • Alix Le Marois17
  • Ekaterina Pazukhina18
  • Sophia Ward19
  • Hubert Slawinski20
  • Marc R. Pelletier14
  • Cian Murphy5
  • Matthew D. Park21
  • Thomas J. A. Snoeks22
  • Alejandro Suárez‐Bonnet23
  • Simon Lawrence Priestnall23
  • Alexandros Hardas24
  • Charlotte Grieco5
  • Ami Archer2
  • Alpkaan Celik2
  • Alejandro Jiménez-Sánchez25
  • Rachel Scott11
  • Hana Zahed26
  • Léa Montégut27
  • Rafael Meza28
  • Clinton H. Durney28
  • Stephen C. Lam29
  • Takahiro Karasaki30
  • Roel C.H. Vermeulen31
  • Huilei Xu32
  • Pablo Serrano‐Fernández33
  • Tatjana Crnogorac‐Jurcevic34
  • Usha Menon35
  • Sophia Apostolidou35
  • Alexey A. Zaikin36
  • Richard Gunu37
  • Harry J. Whitwell38
  • Zhe Huang39
  • Zonglun Li40
  • Xin Hu
  • Bo Zhu
  • Liming Li
  • MD Chirlaque
  • Marcela Guevara
  • Pieter Martijn Kolijn31
  • Aghiles Guenoun26

60 listed; 87 in total.

40 affiliations
  1. 1Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; UKRI UCL Centre for Doctoral Training in AI-enabled Healthcare Systems, University College London, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK
  2. 2Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK
  3. 3Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Cancer Genome Evolution Research Group, University College London Cancer Institute, London, UK
  4. 4Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Division of Medicine, University College London, London, UK
  5. 5Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK
  6. 6Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  7. 7Department of Cell Biology, Albert Einstein College of Medicine, Montefiore Health System, Bronx, New York, NY, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY, USA
  8. 8Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, UK; Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
  9. 9Immunoregulation Laboratory, The Francis Crick Institute, London, UK
  10. 10Autoimmunity Laboratory, The Francis Crick Institute, London, UK
  11. 11Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK
  12. 12Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  13. 13Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Oxford Global Health, University of Oxford, Oxford, UK
  14. 14Novartis, Cambridge, MA, USA
  15. 15Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  16. 16Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  17. 17Tumour Cell Biology Laboratory, The Francis Crick Institute, London, UK
  18. 18Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
  19. 19Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Genomics Science Technology Platform, The Francis Crick Institute, London, UK
  20. 20Genomics Science Technology Platform, The Francis Crick Institute, London, UK
  21. 21Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  22. 22Imaging Research Facility, The Francis Crick Institute, London, UK
  23. 23Department of Pathobiology & Population Sciences, The Royal Veterinary College, London, UK; Experimental Histopathology, The Francis Crick Institute, London, UK
  24. 24Department of Pathobiology & Population Sciences, The Royal Veterinary College, London, UK
  25. 25Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  26. 26Early Detection, Prevention and Infections Branch (EPR), International Agency for Research on Cancer (IARC/WHO), Lyon, France
  27. 27Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  28. 28Department of Population Health Sciences, British Columbia Cancer Research Institute, Vancouver, BC, Canada
  29. 29Department of Basic and Translational Research, British Columbia Cancer Research Institute, Vancouver, BC, Canada
  30. 30Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  31. 31Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands
  32. 32Novartis Biomedical Research, Cambridge, MA, USA
  33. 33Novartis Pharmaceuticals, Basel, Switzerland
  34. 34Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK
  35. 35UCL Innovative Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
  36. 36Department of Mathematics and Institute for Women's Health, University College London, London, UK; Centre for Cognition and Decision making, Institute for Cognitive Neuroscience, HSE University, Moscow, Russia
  37. 37Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
  38. 38National Phenome Centre and Imperial Clinical Phenotyping Centre, Department of Metabolism, Digestion and Reproduction, IRDB, Imperial College London, London, UK; Section of Bioanalytical Chemistry, Burlington Danes Building, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
  39. 39Nuffield Department of Population Health, University of Oxford, Oxford, UK
  40. 40Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, UK; Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
Open at sourceDOICite

Abstract

Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor ( EGFR )-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8 + /claudin4 + alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR , or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

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Cite

BibTeXRIS
BibTeX
@article{pandya2026plasma,
  title = {{Plasma signals of lung tumor promotion for molecular cancer prevention}},
  author = {Tej Pandya and Maria Zagorulya and Michelle M. Leung and Marcellus Augustine and Lydia Liu and Aino‐Maija Leppä and Ulysse Baruchel and Sin Wi Ng and Tamara Klockner and Miriam Mugabo and Anthony J. Griffen and Oleg B. Blyuss and Chrysante S. Iliakis and Amalie Grenov and Kerstin Haase and David C. Muller and K Chan and Jincheng Wu and Vernon A. Burk and Neil Wright and Alix Le Marois and Ekaterina Pazukhina and Sophia Ward and Hubert Slawinski and Marc R. Pelletier and Cian Murphy and Matthew D. Park and Thomas J. A. Snoeks and Alejandro Suárez‐Bonnet and Simon Lawrence Priestnall and Alexandros Hardas and Charlotte Grieco and Ami Archer and Alpkaan Celik and Alejandro Jiménez-Sánchez and Rachel Scott and Hana Zahed and Léa Montégut and Rafael Meza and Clinton H. Durney and Stephen C. Lam and Takahiro Karasaki and Roel C.H. Vermeulen and Huilei Xu and Pablo Serrano‐Fernández and Tatjana Crnogorac‐Jurcevic and Usha Menon and Sophia Apostolidou and Alexey A. Zaikin and Richard Gunu and Harry J. Whitwell and Zhe Huang and Zonglun Li and Xin Hu and Bo Zhu and Liming Li and MD Chirlaque and Marcela Guevara and Pieter Martijn Kolijn and Aghiles Guenoun},
  journal = {Cell},
  year = {2026},
  month = jun,
  doi = {10.1016/j.cell.2026.05.005},
  url = {https://doi.org/10.1016/j.cell.2026.05.005},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Plasma signals of lung tumor promotion for molecular cancer prevention
AU  - Tej Pandya
AU  - Maria Zagorulya
AU  - Michelle M. Leung
AU  - Marcellus Augustine
AU  - Lydia Liu
AU  - Aino‐Maija Leppä
AU  - Ulysse Baruchel
AU  - Sin Wi Ng
AU  - Tamara Klockner
AU  - Miriam Mugabo
AU  - Anthony J. Griffen
AU  - Oleg B. Blyuss
AU  - Chrysante S. Iliakis
AU  - Amalie Grenov
AU  - Kerstin Haase
AU  - David C. Muller
AU  - K Chan
AU  - Jincheng Wu
AU  - Vernon A. Burk
AU  - Neil Wright
AU  - Alix Le Marois
AU  - Ekaterina Pazukhina
AU  - Sophia Ward
AU  - Hubert Slawinski
AU  - Marc R. Pelletier
AU  - Cian Murphy
AU  - Matthew D. Park
AU  - Thomas J. A. Snoeks
AU  - Alejandro Suárez‐Bonnet
AU  - Simon Lawrence Priestnall
AU  - Alexandros Hardas
AU  - Charlotte Grieco
AU  - Ami Archer
AU  - Alpkaan Celik
AU  - Alejandro Jiménez-Sánchez
AU  - Rachel Scott
AU  - Hana Zahed
AU  - Léa Montégut
AU  - Rafael Meza
AU  - Clinton H. Durney
AU  - Stephen C. Lam
AU  - Takahiro Karasaki
AU  - Roel C.H. Vermeulen
AU  - Huilei Xu
AU  - Pablo Serrano‐Fernández
AU  - Tatjana Crnogorac‐Jurcevic
AU  - Usha Menon
AU  - Sophia Apostolidou
AU  - Alexey A. Zaikin
AU  - Richard Gunu
AU  - Harry J. Whitwell
AU  - Zhe Huang
AU  - Zonglun Li
AU  - Xin Hu
AU  - Bo Zhu
AU  - Liming Li
AU  - MD Chirlaque
AU  - Marcela Guevara
AU  - Pieter Martijn Kolijn
AU  - Aghiles Guenoun
PY  - 2026
DA  - 2026/06/01
JO  - Cell
DO  - 10.1016/j.cell.2026.05.005
UR  - https://doi.org/10.1016/j.cell.2026.05.005
AB  - Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor ( EGFR )-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8 + /claudin4 + alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR , or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.
SN  - 0092-8674
SN  - 1097-4172
ER  -