Extended human lymph node explants for evaluation of adaptive immunity

  • Trends Biotechnol. 2025 Aug 29:S0167-7799(25)00302-6. doi: 10.1016/j.tibtech.2025.07.020.
Kanishka Fernando  1 ,  Hong Sheng Quah  2 ,  Lisda Suteja  2 ,  Anne James  3 ,  Fathima F Kuthubudeen  1 ,  Kenny Z Wu  1 ,  Christabella Adine  4 ,  Hariraman Bhuvaneswari  5 ,  Mohanaselvi Senthilkumar  1 ,  Sathiyamoorthy Selvarajan  3 ,  N Gopalakrishna Iyer  6 ,  Eliza L S Fong  7
Affiliations
  • 1. Department of Biomedical Engineering, National University of Singapore, Singapore.
  • 2. Cancer Therapeutics Research Laboratory, National Cancer Center Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore.
  • 3. Anatomical Pathology Department, Singapore General Hospital, Singapore.
  • 4. The N.1 Institute for Health, National University of Singapore, Singapore.
  • 5. Cancer Therapeutics Research Laboratory, National Cancer Center Singapore, Singapore; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 6. Cancer Therapeutics Research Laboratory, National Cancer Center Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore; Department of Head and Neck Surgery, National Cancer Centre Singapore, Singapore. Electronic address: [email protected].
  • 7. Department of Biomedical Engineering, National University of Singapore, Singapore; The N.1 Institute for Health, National University of Singapore, Singapore; Cancer Science Institute, National University of Singapore, Singapore. Electronic address: [email protected].
PMID: 40885665 DOI: 10.1016/j.tibtech.2025.07.020
Abstract

Lymph Nodes (LNs) are a vital component of the adaptive immune system as they have a key role in antigen presentation and regulation of immune responses. However, preclinical models that accurately mimic the complexity and spatial organization of LNs remain a significant unmet need for the study of LN biology. Here, we leveraged the use of biomaterials to significantly extend the lifespan of patient-derived LN explants ex vivo. Hydrogel-embedded LN explants preserved the cellular composition and maintained the intricate spatial organization of the LN. This enabled the LN explants to retain functional responsiveness, as demonstrated by their ability to mount immune responses after exposure to tumor Antigens or SARS-CoV-2 mRNA vaccine. The LN explant models developed in this study offer a robust and physiologically relevant platform for studying immune responses ex vivo, facilitating the development of vaccines and immunotherapies in the context of Cancer and infectious diseases.

Keywords
biomaterials; cancer; hydrogel; immunity; lymph nodes; mRNA vaccine.
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