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A basigin antibody modulates MCTs to impact tumor metabolism and immunity

ABSTRACT: A basigin antibody modulates MCTs to impact tumor metabolism and immunity

PROVIDER: PRJNA1118677 | ENA |

REPOSITORIES: ENA

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A basigin antibody modulates MCTs to impact tumor metabolism and immunity

Project description:Lactate metabolism and signaling intricately intertwine in the context of cancer and immunity. Basigin, working alongside monocarboxylate transporters MCT1 and MCT4, orchestrates the movement of lactate across cell membranes. Despite promising potential in treating aggressive tumors, the impact of basigin antibodies on these interactions remains unclear. Our research sheds light on this complex interplay: basigin positively modulates MCT activity. A basigin antibody transforms basigin into a negative regulator of MCTs. The antibody suppresses lactate transport and enhances anti-tumor immunity in vitro and in vivo. Furthermore, antibody alters metabolic profiles in PDOs-NSCLCs and T cells. Cryo-EM structure analysis and molecular dynamics simulations unveil that MCT1’s turnover rate is influenced by the flexibility of basigin’s Ig2 domain. By restricting Ig2 flexibility, antibody reduces MCT1 turnover. These findings underscore the promise of basigin antibodies in tumor combat by influencing metabolism and immunity and the value of shared ancillary subunits in targeting heteromeric transporters.

2025-05-14 | GSE268751 | GEO

Nano-enabled spatially selective protein degradation modulates lactate metabolism to potentiate antitumor immunity in liver cancer

Project description:Dysregulated cancer metabolism, driven in part by excessive lactate export through monocarboxylate transporter 1 (MCT1) and 4 (MCT4), generates an acidic tumor microenvironment (TME) that suppresses antitumor immunity and impairs therapy. While direct MCT1 and/or MCT4 inhibitors show promise, clinical translation remains limited by systemic toxicity. In this study, we developed polymer-based lysosome-targeting chimeras (LYTACs) that selectively degrade CD147, the MCT1/4 chaperone, in liver cancer cells, reducing lactate efflux in cancer cells while sparing healthy cells, thereby reprogramming lactate metabolism within the TME. We further engineered polymer-based acid-responsive CD147-targeting LYTACs (PARTACs) to achieve controlled intratumoral release under acidic conditions. Systemic administration of PARTACs significantly suppressed tumor progression in several orthotopic liver cancer models. Moreover, PARTACs sensitized tumors to chemo-, immuno-, and radiotherapy with a favorable safety profile. Collectively, our nano-enabled spatially selective strategy modulates lactate metabolism in vivo, augmenting antitumor immunity and improving standard-of-care cancer therapies efficacy.

2026-05-24 | GSE328342 | GEO

Nano-enabled spatially selective protein degradation modulates lactate metabolism to potentiate antitumor immunity in liver cancer

Project description:Nano-enabled spatially selective protein degradation modulates lactate metabolism to potentiate antitumor immunity in liver cancer

| PRJNA1454814 | ENA

Chromatin regulator SMARCAL1 modulates cellular lipid metabolism

Project description:Chromatin regulator SMARCAL1 modulates cellular lipid metabolism

| PRJNA914046 | ENA

Disulfiram treatment suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism

Project description:Antibody responses, involving B cells, CD4+ T cells, and macrophages, are implicated in autoimmune diseases and organ transplant rejection. We have previously shown that inhibiting FROUNT with disulfiram (DSF) suppresses macrophage activation and migration, effectively treating inflammatory diseases. In this study, we investigated the effectiveness of DSF in antibody-producing reactions. Using a heart transplantation mouse model with antibody-mediated rejection, we administered anti-CD8 antibody to exclude cellular rejection. DSF directly inhibited B cell responses in vitro and significantly reduced plasma donor-specific antibodies and graft antibody deposition in vivo, resulting in prolonged survival of the heart graft. DSF also mediated various effects, including decreased macrophage infiltration and increased Foxp3+ regulatory T-cells in the grafts. Additionally, DSF inhibited pyrimidine metabolism-related gene expression induced by B-cell stimulation. These findings demonstrate that DSF modulates antibody production in the immune response complexity by regulating B-cell and macrophage responses.

2024-04-15 | GSE261712 | GEO

Pantothenate metabolism fuels T cell antitumor immunity

Project description:Pantothenate metabolism fuels T cell antitumor immunity

| PRJNA777572 | ENA

Glycerol metabolism modulates antibiotic tolerance in Pseudomonas aeruginosa

Project description:Glycerol metabolism modulates antibiotic tolerance in Pseudomonas aeruginosa

| PRJNA1177469 | ENA

Act1 modulates mRNA metabolism upon IL-17 stimulation

Project description:Act1 modulates mRNA metabolism upon IL-17 stimulation

| PRJNA1099569 | ENA

Impact of glucose metabolism in postnatal cardiomyocytes

Project description:Impact of glucose metabolism in postnatal cardiomyocytes

| PRJNA612444 | ENA

Pre-existing cross-reactive antibody responses do not significantly impact inactivated COVID-19 vaccine-induced neutralization

Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.

2021-10-13 | E-MTAB-11084 | biostudies-arrayexpress

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