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Succinate preserves CD8+ T cell fitness to augment anti-tumor immunity

ABSTRACT: Succinate preserves CD8+ T cell fitness to augment anti-tumor immunity

PROVIDER: PRJNA1271764 | ENA |

REPOSITORIES: ENA

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Succinate preserves CD8+ T cell fitness to augment anti-tumor immunity

Project description:The tricarboxylic acid cycle intermediate succinate accumulates in tumors harboring succinate dehydrogenase (SDH) mutations. Despite evidence that succinate modulates CD8+ T cell cytotoxicity, its influence on T cell differentiation trajectories remains poorly understood. Here we reveal that SDHB-deficient tumors exhibit enriched tumor-specific CD8+ T cell infiltration and enhanced responsiveness to PD-L1 blockade.

2025-08-14 | GSE298906 | GEO

Interleukin-4 modulates type I interferon to augment anti-tumour immunity

Project description:Interleukin-4 modulates type I interferon to augment anti-tumour immunity

| PRJNA1224251 | ENA

Anti-influenza activity of succinate

Project description:In the present study, we discovered an unexpected interplay between immunometabolism and antiviral immunity. Profiling of human bronchial epithelial BEAS-2B cells was performed using Agilent’s SurePrint G3 human gene expression microarray kit. A single-color design provided two types of comparison: (i) IAV-infected versus mock-infected cells, and (ii) succinate-treated infected cells versus mock-infected cells.

2022-02-17 | E-MTAB-10031 | biostudies-arrayexpress

Dietary Succinate Supplementation Alleviates DSS-Induced Colitis via the IL-4Rα/Hif-1α Axis

Project description:Succinate administration induced characteristic type 2 immunity via the tuft cell-ILC2 immune circuit, significantly ameliorating DSS-induced colonic inflammation by enhancing bactericidal capacity, reducing intestinal permeability, and modulating cytokine profiles in the colon. Succinate promoted expansion of myeloid cells in peripheral blood, mesenteric lymph nodes (MLN), and colonic lamina propria. The protective effect of succinate was abolished in Ccr2-/- mice but maintained in Rag1-/- mice. Adoptive transfer of monocytes from succinate-treated donors to naïve recipient mice mitigated intestinal inflammation. RNA-seq revealed increased expression of proinflammatory cytokines IL-1β, IL-6, and lactate upon lipopolysaccharide (LPS) stimulation in monocytes from succinate-treated mice. Moreover, the critical role of the IL-4Rα/Hif-1α axis in succinate-mediated protection was delineated.

2024-02-28 | GSE255272 | GEO

Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis

Project description:Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis

| PRJNA789901 | ENA

Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis

Project description:Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis

| PRJNA822283 | ENA

Interleukin-4 modulates type I interferon to augment anti-tumour immunity [scRNA-Seq]

Project description:Interleukin-4 modulates type I interferon to augment anti-tumour immunity [scRNA-Seq]

| PRJNA1224250 | ENA

Nanoparticle immunoadjuvant complexes augment antigen-specific germinal center responses and enhance humoral immunity

Project description:Nanoparticle immunoadjuvant complexes augment antigen-specific germinal center responses and enhance humoral immunity

| PRJNA1167818 | ENA

Succinate dehydrogenase deficiency-driven succinate accumulation induces drug resistance in acute myeloid leukemia via ubiquitin-cullin regulation

Project description:Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct microenvironment-associated metabolic processes. Here, we identified SDH deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to a wide range of anti-cancer therapies. Mechanistically, succinate promoted the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function was mediated by succinate-triggered upregulation of UBC12 phosphorylation, which impaired its E2 function in cullins neddylation. Notably, decreasing succinate levels by fludarabine could effectively restore the drug sensitivity of SDH-deficient AML PDX. Together, we uncover a novel function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.

2024-08-27 | GSE247623 | GEO

Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis [Bulk]

Project description:Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis [Bulk]

| PRJNA789905 | ENA