Biology subjects

Ilker, N.

Publications and source records attributed to Ilker, N..

4 recordsLinked to original sources

bioRxiv2026

Bifidobacterium pseudocatenulatum extracellular vesicles promote Ly6G+ granulocyte infiltration to inhibit melanoma tumour progression

Harnessing the immunomodulatory capacity of commensal bacteria is an emerging avenue in cancer therapy. Bacterial extracellular vesicles (BEVs) provide a non-replicating, nanoscale alternative to live microbes with the potential for safer systemic delivery. Here, we investigated BEVs from a novel Gram-positive strain of Bifidobacterium pseudocatenulatum (Bif-210). Intravenous administration of Bif-210 BEVs reduced B16-F10 melanoma growth in C57BL/6J mice. Mechanistically, BEVs increased tumour-infiltrating Ly6G+ granulocytes in vivo, increased CD11b+Ly6G+ and ICAM-1+Ly6G+ bone marrow populations, and induced production of the neutrophil-attracting chemokines KC/CXCL1 (mouse) and IL-8 (human). Although Ly6G+ depletion independently inhibited tumour growth, it did not combine additively with BEVs, supporting a model in which Bif-210 BEVs alter Ly6G+ granulocyte function rather than simply expanding a conventional pro-tumour granulocyte pool. BEVs activated TLR2, did not activate TLR4, and upregulated TLR2 on Ly6G+ cells, while proxy assays provided no evidence of NETosis-associated activation. Repeated intravenous BEV administration produced no overt toxicity by tissue histology, body temperature, or body weight monitoring. These findings position B. pseudocatenulatum BEVs as a promising systemic immunotherapy that recruits and re-educates granulocytes via a TLR2-centred pathway to restrain melanoma progression. HIGHLIGHTSO_LIIntravenous Bif-210 BEVs reduce established B16-F10 melanoma growth in mice. C_LIO_LIBif-210 BEVs selectively increase tumour-associated Ly6G+ granulocytes. C_LIO_LIBEV treatment and Ly6G depletion are non-additive, linking BEV activity to granulocyte biology. C_LIO_LIBif-210 BEVs expand Ly6G+ bone marrow populations and induce granulocyte-recruiting chemokines. C_LIO_LIBif-210 BEVs engage TLR2 and enhance granulocyte fitness without NETosis-associated activation. C_LI

cancer biology↗

bioRxiv2026

Systemically delivered Bacteroides thetaiotaomicron-derived bacterial extracellular vesicles inhibit primary and metastatic melanoma growth

The gut microbiome can contribute to anti-tumour immunity and cancer therapy responses, but translating live microbe-based interventions remains challenging due to safety, controllability, and delivery constraints. Bacterial extracellular vesicles (BEVs) are an attractive cell-free alternative, as they package bacterial cargo into a nanoscale format capable of host-cell engagement, immunological activation, and systemic distribution. Here, we investigated the anti-tumour potential of BEVs derived from the human gut commensal Bacteroides thetaiotaomicron (Bt). We show that delivery route is a major determinant of efficacy. Intravenous, but not intraperitoneal, administration produced robust anti-tumour activity in a B16F10 melanoma mouse model. Intravenously delivered Bt BEVs suppressed primary tumour growth in a dose-dependent manner and reduced metastatic outgrowth in the lung. Bt BEVs did not directly impair tumour-cell viability in vitro, but they activated NF-{kappa}B and Toll-like receptor signalling in innate immune reporter systems and localised to tumour tissue following systemic administration. Together, these data support a model in which Bt BEVs act via host immune modulation rather than direct tumour cytotoxicity. These findings identify naturally produced commensal-derived Bt BEVs as a potential microbial therapeutic modality and as an alternative to the use of live bacterial administration in cancer therapy.

cancer biology↗

bioRxiv2025

Neuropilin 2 stabilises adherens junctions and protects against endothelial activation by promoting the interaction between VE cadherin and p120 catenin

The mechanosensing properties of endothelial cell-cell junctions are essential for vascular beds to respond to the mechanical forces exerted by blood flow. In states of disturbed flow, endothelial cells (ECs) become activated and transition to a pro-inflammatory, atheroprone phenotype. Here, we investigated the role of transmembrane glycoprotein neuropilin 2 (NRP2) in maintaining adherens junction integrity using cultured immortalised mouse ECs and a genetically modified mouse model to demonstrate the effects of an endothelial-specific deletion of Nrp2 in vivo. We reveal that, akin to its ortholog, Nrp1, Nrp2 exists as a constituent of adherens junctions, maintaining surface availability of VE cadherin by promoting its interaction with p120 catenin. As a consequence, endothelial knockout mice (Nrp2flfl.ECKO) display hyperpermeable retinal vasculature during development. Nrp2 depletion was subsequently found to activate key pro-inflammatory cytokines and adhesion molecules known to participate in the progression of atherogenesis, in addition to increased immune cell attachment aortic plaque development. These findings describe a role for Nrp2 in maintaining junctional signalling in ECs, protecting against endothelial activation during a state of vascular disease.

cell biology↗

bioRxiv2024

Bifidobacterium pseudocatenulatum capsular exopolysaccharide enhances systemic anti-tumour immunity in pre-clinical breast cancer

Gut microbes have merged as powerful regulators of cancer responses, with Bifidobacterium species and strains playing a key role in promoting anti-tumour immunity. While they represent promising candidates for cancer therapeutics, the specific underlying microbial mechanisms driving their efficacy remains poorly understood. In this study, we demonstrate the broad potential of Bifidobacterium species to inhibit breast cancer progression across multiple pre-clinical mouse models. We identify a novel strain, Bifidobacterium pseudocatenulatum 210, which induces systemic anti-tumour immunity and enhances responses to standard-of-care therapies via its cell surface capsular exopolysaccharide (EPS). B. pseudocatenulatum 210 EPS promotes dendritic cell activation and increases systemic cDC1 infiltration, leading to robust CD8+ T cell-mediated anti-tumour activity. Our findings position Bifidobacterium EPS as a novel class of therapeutic compounds with significant potential for cancer treatment.

cancer biology↗