Whole-body cellular mapping in mouse using standard IgG antibodies

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(4), P. 617 - 627

Published: July 10, 2023

Abstract Whole-body imaging techniques play a vital role in exploring the interplay of physiological systems maintaining health and driving disease. We introduce wildDISCO, new approach for whole-body immunolabeling, optical clearing mice, circumventing need transgenic reporter animals or nanobody labeling so overcoming existing technical limitations. identified heptakis(2,6-di- O -methyl)-β-cyclodextrin as potent enhancer cholesterol extraction membrane permeabilization, enabling deep, homogeneous penetration standard antibodies without aggregation. WildDISCO facilitates peripheral nervous systems, lymphatic vessels immune cells whole mice at cellular resolution by diverse endogenous proteins. Additionally, we examined rare proliferating effects biological perturbations, demonstrated germ-free mice. applied wildDISCO to map tertiary lymphoid structures context breast cancer, considering both primary tumor metastases throughout mouse body. An atlas high-resolution images showcasing nervous, vascular is accessible http://discotechnologies.org/wildDISCO/atlas/index.php .

Language: Английский

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Localization, tissue biology and T cell state — implications for cancer immunotherapy

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(12), P. 807 - 823

Published: May 30, 2023

Language: Английский

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Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas

Gut, Journal Year: 2023, Volume and Issue: 72(10), P. 1927 - 1941

Published: May 25, 2023

To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored relevance T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for generation local antitumour immunity.We characterised functional states spatial organisation PDAC-infiltrating cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling microdissected TLSs, as well in vitro assays. In addition, performed a pan-cancer analysis tumour-infiltrating scRNA-seq sc receptor datasets from eight cancer types. evaluate clinical our findings, used PDAC bulk RNA-seq data The Cancer Genome Atlas PRINCE chemoimmunotherapy trial.We found that subset PDACs harbours fully developed TLSs where proliferate differentiate plasma cells. These mature also support activity are enriched with tumour-reactive Importantly, showed chronically activated, exposed to fibroblast-derived TGF-β may act TLS organisers by producing chemoattractant CXCL13. Identification highly similar subsets clonally expanded CXCL13+ across multiple types further indicated conserved link between tumour-antigen recognition allocation within sheltered hubs tumour microenvironment. Finally, signature reflecting was pretreatment biopsies patients longer survival after receiving different regimens.We provided framework understanding biological role PDAC-associated revealed their potential guide selection future immunotherapy trials.

Language: Английский

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Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives

The Innovation, Journal Year: 2023, Volume and Issue: 4(6), P. 100503 - 100503

Published: Aug. 29, 2023

•Insights into the intricate facets of immune microenvironment hold key to pioneering clinical strategies in combatting bacterial infections.•The design principles for antimicrobial biomaterials vary depending on at different stages infection.•Immunomodulatory display robust efficacy and vaccine attributes animals trials, promising intractable infections. Bacterial infectious diseases are one leading causes death worldwide. Even with use multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant infections 2019. By 2050, number deaths will reach 10 annually. The increasing mortality may be partly due heterogeneity infection microenvironment, such as bacteria, biofilms, persister cells, intracellular small colony variants. In addition, complexity makes direct activity unsatisfactory long-term chronic attributed failing modulate active action cells. Therefore, there is an urgent need effective alternatives treat Accordingly, development immunomodulatory has recently received considerable interest; however, a comprehensive review their research progress lacking. this review, we focus mainly future perspectives used infection. First, describe characteristics acute phases Then, highlight corresponding advantages disadvantages. Moreover, discuss biomaterial-mediated vaccines' potential applications challenges activating innate adaptive memory. This serve reference studies develop next-generation accelerate translation practice.

Language: Английский

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Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(11), P. 1852 - 1870.e9

Published: Oct. 12, 2023

Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays progenitor (Tpex) phenotype and correlates complete response to ICB. We validate Tex-SPRY1 as an ICB-specific predictor improved survival using independent ICB-/non-ICB cohorts demonstrate expression enforces Tpex enhances ICB efficacy. Additionally, contribute proinflammatory macrophages functional state B cells, which thereby promotes antitumor immunity by enhancing effector functions. Overall, our findings unravel progenitor-like cells' role effective responses for inform mechanistic biomarkers future individualized immunotherapy.

Language: Английский

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