{"title":"Engineering Tertiary Lymphoid Structures: Nanomedicine, Bioengineering, and Biomaterials for Precision Immunotherapy","authors":"Shaza Karaman, Mei ElGindi, Jeremy Teo","doi":"10.1002/anbr.202500220","DOIUrl":null,"url":null,"abstract":"<p>Tertiary lymphoid structures (TLSs) are inducible, ectopic aggregates that mirror the architecture and immunological functions of secondary lymphoid organs, arising in nonlymphoid tissues during chronic inflammation, infection, autoimmunity, and cancer. Their ability to orchestrate local antigen presentation, lymphocyte activation, and germinal center reactions supports their critical roles in both protective immunity and disease pathogenesis. Recent breakthroughs in biomaterials science and nanotechnology have enabled the rational design and manipulation of the stromal and molecular microenvironmental cues necessary for TLS neogenesis, maturation, and modulation. This review collates recent advances in TLS biology with the latest developments in engineering strategies, including the use of hydrogels as scaffolding matrices, nanoparticles, and other microstructured materials, aimed at inducing, supporting, or modulating TLS both in vivo and in vitro. This review critically assess how material properties, cytokine delivery, and cellular engineering can recapitulate or enhance key stromal–immune interactions that drive TLS formation. Furthermore, the translational implications of biomaterial- and nanoparticle-based TLS engineering are examined, highlighting preclinical applications in cancer immunotherapy, autoimmune disorders, and tissue regeneration. Finally, major challenges and future perspectives toward utilizing engineered TLS as customizable, site-specific immunotherapeutic platforms for precision medicine are discussed.</p>","PeriodicalId":29975,"journal":{"name":"Advanced Nanobiomed Research","volume":"6 4","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/anbr.202500220","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Nanobiomed Research","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/anbr.202500220","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/16 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Tertiary lymphoid structures (TLSs) are inducible, ectopic aggregates that mirror the architecture and immunological functions of secondary lymphoid organs, arising in nonlymphoid tissues during chronic inflammation, infection, autoimmunity, and cancer. Their ability to orchestrate local antigen presentation, lymphocyte activation, and germinal center reactions supports their critical roles in both protective immunity and disease pathogenesis. Recent breakthroughs in biomaterials science and nanotechnology have enabled the rational design and manipulation of the stromal and molecular microenvironmental cues necessary for TLS neogenesis, maturation, and modulation. This review collates recent advances in TLS biology with the latest developments in engineering strategies, including the use of hydrogels as scaffolding matrices, nanoparticles, and other microstructured materials, aimed at inducing, supporting, or modulating TLS both in vivo and in vitro. This review critically assess how material properties, cytokine delivery, and cellular engineering can recapitulate or enhance key stromal–immune interactions that drive TLS formation. Furthermore, the translational implications of biomaterial- and nanoparticle-based TLS engineering are examined, highlighting preclinical applications in cancer immunotherapy, autoimmune disorders, and tissue regeneration. Finally, major challenges and future perspectives toward utilizing engineered TLS as customizable, site-specific immunotherapeutic platforms for precision medicine are discussed.
期刊介绍：
Advanced NanoBiomed Research will provide an Open Access home for cutting-edge nanomedicine, bioengineering and biomaterials research aimed at improving human health. The journal will capture a broad spectrum of research from increasingly multi- and interdisciplinary fields of the traditional areas of biomedicine, bioengineering and health-related materials science as well as precision and personalized medicine, drug delivery, and artificial intelligence-driven health science.
The scope of Advanced NanoBiomed Research will cover the following key subject areas:
▪ Nanomedicine and nanotechnology, with applications in drug and gene delivery, diagnostics, theranostics, photothermal and photodynamic therapy and multimodal imaging.
▪ Biomaterials, including hydrogels, 2D materials, biopolymers, composites, biodegradable materials, biohybrids and biomimetics (such as artificial cells, exosomes and extracellular vesicles), as well as all organic and inorganic materials for biomedical applications.
▪ Biointerfaces, such as anti-microbial surfaces and coatings, as well as interfaces for cellular engineering, immunoengineering and 3D cell culture.
▪ Biofabrication including (bio)inks and technologies, towards generation of functional tissues and organs.
▪ Tissue engineering and regenerative medicine, including scaffolds and scaffold-free approaches, for bone, ligament, muscle, skin, neural, cardiac tissue engineering and tissue vascularization.
▪ Devices for healthcare applications, disease modelling and treatment, such as diagnostics, lab-on-a-chip, organs-on-a-chip, bioMEMS, bioelectronics, wearables, actuators, soft robotics, and intelligent drug delivery systems.
with a strong focus on applications of these fields, from bench-to-bedside, for treatment of all diseases and disorders, such as infectious, autoimmune, cardiovascular and metabolic diseases, neurological disorders and cancer; including pharmacology and toxicology studies.
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