Nanobody immunolabelling and three-dimensional imaging reveals spatially restricted LYVE1 expression by kidney lymphatic vessels in mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 9, 2024

Lymphatic vessels are complex three-dimensional (3D) structures that facilitate tissue fluid clearance and regulate immune responses in health inflammatory contexts. Recent advances wholemount immunolabelling 3D imaging have provided insights into organ-specific heterogeneity of lymphatic structure function. However, the visualisation deep within an intact organ remains a challenge. We hypothesised nanobodies, single-domain antibodies raised camelid species, would result improved labelling lymphatics mouse organs, without loss information due to sectioning or inadequate penetration. generated characterised nanobody clones targeting vessel endothelial hyaluronan receptor 1 (LYVE1), marker capillaries. Nanobodies were superior at penetrating whole organs enhanced compared with conventional anti-LYVE1 polyclonal antibody. Utilising this new tool, we found kidney lymphatics; which is challenging, spatially restricted LYVE1 expression skin, heart, lung. The timing spatial restriction coincides early postnatal period mice. Our findings highlight unexpected, characteristic vessels, whilst providing novel experimental tool for characterisation, isolation, perturbation disease.

Язык: Английский

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Peptide Antigen‐Surfaced TLR9‐Adjuvanting Nanovaccines as a Versatile Therapeutic Modality to Eradicate Acute Myeloid Leukemia

Advanced Functional Materials, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 24, 2024

Abstract Peptide antigen vaccines constitute a promising clinical strategy for treating cancer patients. However, their anticancer immune response remains modest because of the suboptimal presentation peptide antigens and/or insufficient activation antigen‐presenting cells (APCs). The development therapeutic acute myeloid leukemia (AML) poses an even greater challenge AML disseminate throughout body. In this study, antigen‐surfaced TLR9‐adjuvanting nanovaccines (PASTA‐NV), which display multiple Wilm's tumor 1 (WT1) peptides on surface and encapsulate CpG ODN adjuvants within watery interior to simultaneously increase APC activation/proliferation, are reported. Interestingly, systemic administration PASTA‐NV induces strong cellular humoral responses in orthotopic murine MLL‐AF9 models. When combined with anti‐CTLA4 antibody, achieves complete regression mouse models establishes durable anti‐AML immunity, effectively resisting rechallenge leukemic cells. provides new general avenue induce robust specific has potential revive antigen‐based therapy.

Язык: Английский

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IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Lymphatic vessels play a crucial role in activating anti-tumor immune surveillance but also contribute to metastasis and systemic tumor progression. Whether distinct lymphatic phenotypes exist that govern the switch between immunity remains unclear. Here we reveal cytotoxic normalizes function uncouples metastatic potential. We find mice humans, intratumoral vessel density negatively correlates with productive responses identify IFNγ as an intrinsic inhibitor of lymphangiogenesis. Specific deletion

Язык: Английский

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Biomechanical regulation of anti-tumor immune responses in the TME

Elsevier eBooks, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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