Engineering the Deformability of Albumin‐Stabilized Emulsions for Lymph‐Node Vaccine Delivery

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(26)

Published: May 19, 2021

Abstract A major challenge in vaccine delivery is to achieve robust lymph‐node (LN) accumulation, which can capitalize on concentrated immunocytes and cytokines LNs stimulate the onset persistence of adaptive immune responses. Previous attempts at developing systems have focused sizes, charges, or surface ligands but not their deformability. In fact, LN homing antigen‐presenting cells depends deformability pass through cellular gaps. Herein, albumin‐stabilized emulsions engineered. Owing self‐adaptive deformability, droplets (≈330 nm) attach deform between adjust sizes endothelial gaps (20–100 nm), favoring direct transfer (intercellular pathway). Additionally, owing relatively large some be retained administration sites for potent antigen uptake activation APCs as well LN‐targeted vaccines (intracellular Compared with solid particles, dual strategy evidently enhances accumulation drainage, potently stimulates responses, increases survival rate tumor‐bearing mice. Thus, may offer an efficient targeting enhanced vaccinations.

Language: Английский

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The pre-metastatic niche in lymph nodes: formation and characteristics

Cellular and Molecular Life Sciences, Journal Year: 2021, Volume and Issue: 78(16), P. 5987 - 6002

Published: July 9, 2021

Abstract Lymph node metastasis is a crucial prognostic parameter in many different types of cancers and gateway for further dissemination to distant organs. Prior metastatic dissemination, the primary tumor prepares remodeling draining (sentinel) lymph by secreting soluble factors or releasing extracellular vesicles that are transported lymphatic vessels. These important changes occur before appearance first cell create what known as pre-metastatic niche giving rise subsequent survival growth cells. In this review, structure, matrix composition emerging heterogeneity cells forming it described. Current knowledge major cellular molecular processes associated with nodal formation, including lymphangiogenesis, remodeling, immunosuppressive enlisting nodes additionally summarized. Finally, future directions research could possibly take clinical impact discussed.

Language: Английский

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The metabolism-modulating activity of IL-17 signaling in health and disease

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(5)

Published: April 5, 2021

IL-17 was discovered nearly 30 yr ago, but it has only been recently appreciated that a key function of this cytokine is to orchestrate cellular and organismal metabolism. Indeed, metabolic regulation integrated into both the physiological pathogenic aspects responses. Thus, understanding interplay between downstream processes could ultimately inform therapeutic opportunities for diseases involving IL-17, including some not traditionally linked pathway. Here, we discuss emerging pathophysiological roles related metabolism, signal transduction.

Language: Английский

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FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure

Science Advances, Journal Year: 2021, Volume and Issue: 7(29)

Published: July 16, 2021

Foxc2 sustains adult lymphatic vascular specialization and coordinates organ-specific lymph flow, gut microbiota, inflammation.

Language: Английский

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Communication, construction, and fluid control: lymphoid organ fibroblastic reticular cell and conduit networks

Trends in Immunology, Journal Year: 2021, Volume and Issue: 42(9), P. 782 - 794

Published: Aug. 3, 2021

FRCs use polarized microtubule networks to direct the secretion of ECM components and construct mammalian conduit network.The network functions as a filter that monitors fluid draining peripheral tissues, an export system for systemic dissemination locally produced molecules including antibodies.Emerging evidence indicates there are mechanosensitive mechanisms control flow through secondary lymphoid organs, important tissue homeostasis immune function.Fluid systems is robust, remains functional throughout perturbation lymph node expansion in response immunogenic challenges. Fibroblastic reticular cells (FRCs) crucial part stromal cell infrastructure organs (SLOs). Lymphoid organ fibroblasts form specialized niches interactions thereby govern lymphocyte activation differentiation. Moreover, produce ensheath extracellular matrix (ECM) microfibers called system. FRC-generated conduits contribute by funneling fluids containing antigens inflammatory mediators SLOs. We review recent progress FRC biology has advanced our understanding interactions. discuss intricate relationships between cellular fibrillar networks, which together basis efficient communication tissues they survey. The fundamental problem reproducing at one point either exactly or approximately message selected another point. … significant aspect actual from set possible messages. must be designed operate each selection, not just will actually chosen since this unknown time design (C.E. Shannon [1.Shannon C.E. A mathematical theory communication.Bell System Tech. J. 2021; 27: 379-423Crossref Scopus (19817) Google Scholar]). coordinated different populations facilitate recognition pathogens cancer precisely orchestrate balance regulation. establishment maintenance relies on accurate transmission information inner outer body surfaces diverse populations. According Shannon's work radio signals 1940s Scholar], data composed three elements: source data, channel, receiver. 'communication' – expressed receiver able identify what were generated source, based signal received channel. At conceptual level (and paraphrasing concept), 'information' can defined resolution uncertainty. In other words, analogous loss systems, also known entropy, requires dedicated means protocols secure optimal communication. least partially resolved uncertainty processes underlying regulation innate adaptive hubs we highlight findings how fibroblast non-cellular (ECM; see Glossary) combine transfer current state-of-the-art fibroblastic research help further elucidate essential rules engagement SLOs, namely splenic white pulp, nodes (LNs), Peyer's patches, permanent structures during embryonic postnatal development present [2.Onder L. Ludewig B. fresh view LN organogenesis.Trends Immunol. 2018; 39: 775-787Abstract Full Text PDF PubMed (0) Scholar]. basic principles SLO architecture interaction microenvironments such antigen-sampling zone, adjacent B follicles, T egress zone (Figure 1A , Key figure). Immune congregate SLOs because possess specific blood vascular entry channels, appear, LNs postcapillary venules termed high endothelial (HEVs) [3.Ager A. High vessels: critical regulators function.Front. 2017; 8: 45Crossref (60) recirculating access via shown activated entering subcapsular sinus [4.Thomas S.N. et al.Implications lymphatic transport immunity immunotherapy.Annu. Rev. Biomed. Eng. 2016; 18: 207-233Crossref pulp marginal [5.Lewis S.M. al.Structure function spleen.Sci. 2019; 4eaau6085Crossref Crucial occur spatially priming naïve dendritic [6.Krishnamurty A.T. Turley S.J. cells: cartographers system.Nat. 2020; 21: 369-380Crossref instruction helper (Th) T–B border, affinity maturation antibodies germinal center reaction [7.Pikor N.B. al.Development immunological cells.J. 206: 257-263Crossref Thus, processing immunologically relevant surfaces, among cells, ensured standard functionally equivalent environments. principal act molecular screening fluids, exemplified LNs, integral maintain [8.Moore J.E. Bertram C.D. Lymphatic flows.Annu. Fluid Mech. 50: 459-482Crossref (73) liquid all collected initial vessels contain primary flap valves, permit collection interstitial while simultaneously preventing intralymphatic leaking out [9.Ikomi F. al.Interstitial fluid, plasma protein, colloid, leukocyte uptake into lymphatics.J. Appl. 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Cell. 23: 1203-1218Abstract (113) reduction IgM+ spleens lacking expression PLVAP (PlvapECKO−Tie2) relative wild-type Likewise, PVLAP controls lymphocytes soluble parenchyma, evidenced immigration popliteal (pLNs), was almost threefold higher KO (Plvap−/−) compared [24.Rantakari P. LNs.Nat. 2015; 16: 386-396Crossref within closely linked liquids compartments. structural scaffold microenvironmental harbor sets formed fibroblasts, referred Scholar,7.Pikor Scholar,25.Fletcher A.L. niche tissues.Curr. Opin. 64: 110-116Crossref 1B). generate proteins uniquely arranged fibrillary mesh [26.Gretz al.Cords, corridors conduits: architectural elements cortex.Immunol. 2005; 156: 11-24Crossref (326) Scholar,27.Novkovic al.Topological structure robustness Conduit system.Cell Rep. 30: 893-904Abstract exhibit apicobasal polarity [28.Martinez V.G. al.Fibroblastic deposition expansion.Cell 29: 2810-2822Abstract completely conduits. Original tracer studies rat determined filters channels venous vasculature 1B) [29.Anderson A.O. Anderson N.D. Studies microvasculature normal LNs.Am. Pathol. 1975; 80: 387-418PubMed nexus Distinct underpin positioning factors IL-7 [30.Link regulate naive cells.Nat. 1255-1265Crossref BAFF [31.Cremasco V. al.B follicle confines governed 2014; 15: 973-981Crossref (155) differentiation [32.Rodda L.B. al.Single-cell RNA sequencing niche-associated heterogeneity.Immunity. 48: 1014-1028Abstract across grouped according interact anatomical location For instance, (MRCs) follicular (FDCs) build center, border (TBRCs) Th (TRCs) DC–T interactions, (PRCs) connect definition subsets, well been recently discussed briefly summarized (see Figure I Box 1). However, universal every subset ability classical organize Scholar,33.Malhotra D. al.Transcriptional profiling inflamed resting defines hallmarks.Nat. 13: 499-510Crossref focus here generation, construction network, contributes it impacts homeostatic conditions inflammation.Box 1Paradigmatic transcriptomicsThe term first used 1968 when thin filamentous traversing [98.Nossal G.J. al.Antigens immunity. XV. Ultrastructural features capture follicles.J. 1968; 127: 277-290Crossref [99.Hanna M.G. Szakal A.K. 125I-labeled centers mouse spleen: histologic ultrastructural autoradiographic reaction.J. 101: 949-962PubMed described. Fibroblasts showing these particular topological properties found [100.Nicander al.Ontogeny ileal sheep goats.Am. Anat. 1991; 237-249Crossref most common description still podoplanin (PDPN) absence marker CD31 Genetic targeting models, example, signature chemokine (Ccl19–cre) [101.Chai Q. al.Maturation myofibroblastic precursors immunity.Immunity. 2013; 38: 1013-1024Abstract Scholar,102.Onder initiation organogenesis.Immunity. 47: 80-92Abstract permits elaboration developmental origin, dynamics, vivo. transcriptomic analyses provided high-resolution maps heterogeneity trajectories Scholar,91.Cheng H.-W. al.Origin pulp.Nat. 1739Crossref (24) Scholar,92.Prados lineage convergence governs immunity.Nat. 22: 510-519Crossref (2) Scholar,103.Perez-Shibayama C. al.Type interferon signaling prevents exhaustive CD8+ cells.Sci. 5eabb7066Crossref 104.Pezoldt al.Neonatally imprinted induce tolerogenic mesenteric 9: 3903-3914Crossref 105.Pikor al.Remodeling light dark 649-659Crossref 106.Kapoor V.N. al.Gremlin 1+ maintains tissues.Nat. 571-585Crossref (5) IA). major assigned correspond regions (MRCs), follicles (FDCs), borders (TBRCs), zones (TRCs), space (PRC). medulla, compartment unique SLO, harbors additional, largely medullary (MedRCs) [103.Perez-Shibayama Scholar,107.Huang H.-Y. al.Identification new involved regulating homeostasis.PNAS. 115: E6826-E6835Crossref overlapping gene signatures gradients reflect IB). MRCs express Madcam1, Tnfsf11 (encoding RANKL), Cxcl13, whereas FDCs equipped complement Fc receptors complexes example Cr2 Fcer2a. TBRCs low Cxcl12, Ccl19, Ccl21a, TRCs highest Il7 PRCs surrounding Cd34, Ly6a, Pdgfrb markers associated stemness precursor potential [91.Cheng Scholar,93.Krautler N.J. al.Follicular emerge ubiquitous precursors.Cell. 150: 194-206Abstract (242) genes encoding forming conduits, Col1a1, Col4a1, Dcn, elaborating pathways, providing growth niches, display regula

Language: Английский

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Molecular and clinical diversity in primary central nervous system lymphoma

Annals of Oncology, Journal Year: 2022, Volume and Issue: 34(2), P. 186 - 199

Published: Nov. 17, 2022

Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell presenting with variable response rates probably to underlying molecular heterogeneity.To identify characterize PCNSL heterogeneity facilitate clinical translation, we carried out comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation features] in discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs validation formalin-fixed, paraffin-embedded (FFPE) 93 RNA-seq clinico-radiological data.Consensus clustering data uncovered concordant classification four robust, non-overlapping, prognostically significant clusters (CS). The CS1 CS2 groups presented an immune-cold hypermethylated profile but behavior. 'immune-hot' CS4 group, enriched mutations increasing the Janus kinase (JAK)-signal transducer activator transcription (STAT) nuclear factor-κB activity, had most favorable outcome, while heterogeneous-immune CS3 group worse prognosis due its association meningeal infiltration HIST1H1E mutations. was characterized by high Polycomb repressive complex 2 activity CDKN2A/B loss leading higher proliferation activity. Integrated on proposed targets suggests potential use immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) CS1, lenalidomide/demethylating drugs CS2, enhancer zeste polycomb subunit (EZH2) CS3. We developed algorithm subtypes using from either FFPE or FF tissue.The integration genome-wide revealed patterns distinctive prognostic impact that provides basis future stratification subtype-based targeted interventions.

Language: Английский

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Nanovaccine-based strategies for lymph node targeted delivery and imaging in tumor immunotherapy

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 23, 2023

Abstract Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific adverse side effects. However, challenge field of therapeutic is ensuring delivery components to lymph nodes (LNs) activate cells. The clinical response rate traditional falls short expectations due inadequate node delivery. With rapid development nanotechnology, a large number nanoplatform-based LN-targeting nanovaccines been exploited for optimizing immunotherapies. In addition, some possess non-invasive visualization performance, which benefit understanding kinetics nanovaccine exposure LNs. Herein, we present parameters nanoplatforms, such as size, surface modification, shape, deformability, affect functions nanovaccines. recent advances nanoplatforms with different promoting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies both improve targeting performance enhance quality LN discussed. Finally, summarize prospects challenges /or strategies, optimize efficacy

Language: Английский

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Advances in photoacoustic imaging aided by nano contrast agents: special focus on role of lymphatic system imaging for cancer theranostics

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 20, 2023

Photoacoustic imaging (PAI) is a successful clinical platform for management of cancer and other health conditions that has seen significant progress in the past decade. However, translation PAI based methods are still under scrutiny as quality information derived from PA images not on par with methods. Hence, to improve PAI, exogenous contrast agents, form nanomaterials, being used achieve better image less side effects, lower accumulation, improved target specificity. Nanomedicine become inevitable management, it contributes at every stage diagnosis therapy, surgery, even postoperative care surveillance recurrence. Nanocontrast agents have been developed explored early diagnosis. The systemic stability specificity nanomaterials render its theranostic property depends various influencing factors such administration route physico-chemical responsiveness. recent focus targeting lymphatic system nodes diagnosis, they play vital role progression metastasis. This review aims discuss advancements using nanoparticles theranostics emphasis progression, metastasis, guided tumor resection, finally drug delivery.

Language: Английский

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Same yet different — how lymph node heterogeneity affects immune responses

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(5), P. 358 - 374

Published: Dec. 14, 2023

Language: Английский

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Advances in nanomedicines for lymphatic imaging and therapy

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 24, 2023

Abstract Lymph nodes play a pivotal role in tumor progression as key components of the lymphatic system. However, unique physiological structure lymph has traditionally constrained drug delivery efficiency. Excitingly, nanomedicines have shown tremendous advantages node-specific delivery, enabling distinct recognition and diagnosis nodes, hence laying foundation for efficient therapies. In this review, we comprehensively discuss factors affecting specific enrichment systematically summarize precise node therapeutic application, including treatment nanodrugs imaging identification Notably, delve into critical challenges considerations currently facing nanomedicines, futher propose effective strategies to address these issues. This review encapsulates recent findings, clinical applications, future prospects designing nanocarriers system targeting, with potential implications improving cancer strategies.

Language: Английский

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