4.5 Article

A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

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NATURE CANCER
卷 3, 期 6, 页码 696-+

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NATURE PORTFOLIO
DOI: 10.1038/s43018-022-00376-z

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资金

  1. Wellcome Trust [203141/Z/16/Z]
  2. Common Fund of the Office of the Director of the National Institutes of Health
  3. NCI
  4. NHGRI
  5. NHLBI
  6. NIDA
  7. NIMH
  8. NINDS
  9. Wellcome Trust Clinical Research Career Development Fellowship [220589/Z/20/Z]
  10. Academy of Medical Sciences Starter Grant for Clinical Lecturers
  11. National Institute for Health Research (NIHR) Academic Clinical Lectureship
  12. NIHR University College London Hospitals Biomedical Research Centre
  13. ideas 2 innovation translation scheme at the Francis Crick Institute
  14. Breast Cancer Research Foundation (BCRF)
  15. Cancer Research UK (CRUK) Early Detection and Diagnosis Project award
  16. CRUK
  17. NIHR
  18. Rosetrees Trust
  19. UKI NETs
  20. Francis Crick Institute from CRUK [FC001169]
  21. UK Medical Research Council [FC001169]
  22. CRUK Lung Cancer Centre of Excellence [C11496/A30025]
  23. Butterfield Trust
  24. Stoneygate Trust
  25. NovoNordisk Foundation [16584]
  26. Royal Society Professorship Enhancement Award [RP/EA/180007]
  27. NIHR Biomedical Research Centre at University College London Hospitals
  28. CRUK-University College London Centre
  29. Experimental Cancer Medicine Centre
  30. BCRF
  31. Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant [SU2C-AACR-DT23-17]
  32. European Research Council (ERC) under the European Union [FP7/2007-2013, FP7-THESEUS-617844]
  33. European Commission ITN [FP7-PloidyNet 607722]
  34. ERC Advanced Grant (PROTEUS) from the ERC under the European Union's Horizon 2020 research and innovation program [835297]
  35. Chromavision from the European Union's Horizon 2020 research and innovation program [665233]
  36. Wellcome Trust [220589/Z/20/Z] Funding Source: Wellcome Trust

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This study demonstrates the presence of resident V delta 1 gamma delta T cells in human lung tissues, particularly enriched in lung tumors with memory and effector phenotypes. The intratumoral V delta 1 T cells exhibit stem-like features and immune functions beneficial to the patient post-surgery. Integrating V delta 1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer is of great importance.
Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of V delta 1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission. Murine tissues harbor signature gamma delta T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident gamma delta cells are less well defined. In the present study, we show that human lung tissues harbor a resident V delta 1 gamma delta T cell population. Moreover, we demonstrate that V delta 1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral V delta 1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8(+) T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA(-)CD27(-) effector memory V delta 1 T cells in tumors and, most strikingly, with the numbers of CD103(+) tissue-resident V delta 1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating V delta 1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer.

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