Ontology highlight
ABSTRACT:
PROVIDER: PRJNA993180 | ENA |
REPOSITORIES: ENA
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Project description:A single-cell analysis of the NK cell landscape reveals that dietary restriction boosts NK cell antitumor immunity via Eomesdermin
| PRJNA1049009 | ENA
Project description:Natural killer (NK) cells are primarily responsible for tumor surveillance, and their activation entirely depends on optimal metabolic signals. The adaptation of NK cell anti-tumor responses to nutritional stress is still poorly understood. Here, based on single-cell RNA sequencing, we discovered that dietary restriction (DR) enriches the rejuvenated subset of CD27+CD11b+ NK cells and improves their activation via Eomesodermin (Eomes), a transcription factor upregulated during DR treatment. Eomes reverses the differentiation of rejuvenated to senescent NK cells by antagonizing the T-bet-Zeb2 axis while improving chemotaxis and adhesion. Furthermore, DR increases the chromatin accessibility of Eomes to genes that regulate chemotaxis and adhesion in NK cells. To summarize, tumor control under dietary restriction requires Eomes-regulated NK cell anti-tumor immunity.
2024-01-01 | GSE249425 | GEO
Project description:Transcription profiling by array of Drosophila after dietary restriction
2014-07-14 | E-GEOD-16738 | ExpressionAtlas
Project description:Fasting has long been associated with the improved elimination of cancer cells. However, the distinctive role of specific immune subsets mediating these anti-tumor properties remain elusive. Using a cyclic fasting diet (CFD) after tumor initiation, we investigated the impact of fasting on NK cell anti-tumor immunity. We found that adherence to a CFD improved anti-tumor immunity against both solid and metastatic tumors in a NK cell-dependent manner. During periods of fasting, NK cells underwent tissue redistribution where NK cells in the spleen experienced tissue-specific metabolic rewiring. These NK cells were exposed to elevated concentrations of fatty acids and glucocorticoids which increased fatty acid metabolism via expression of CPT1A, and was essential for NK cell survival and anti-tumor functions. In parallel, a population of NK cells were redistributed to the bone marrow during CFD in a S1PR5- and CXCR4-dependent manner. These cells were primed by an increased pool of IL-12-expressing myeloid cells which improved IFN-g production. Together, these data uncover a novel dietary strategy to improve tumor clearance and identifies a previously unknown mechanistic link between dietary restriction and optimized innate immune responses.
2024-10-28 | GSE267467 | GEO
Project description:BPTF Depletion Enhances NK Cell Mediated Antitumor Immunity
| PRJNA339273 | ENA
Project description:Dietary methionine restriction impairs anti-tumor immunity through gut microbiota
| PRJNA751076 | ENA
Project description:Calorie/Dietary Restriction and Resveratrol in Female Drosophila Melanogaster Head/Thorax
2014-07-03 | E-GEOD-26724 | ExpressionAtlas
Project description:Natural killer (NK) cells play pivotal roles in antitumor immunity, yet their connection to tumor metabolism remains unclear. Our systematic analysis of multiomics data and survival data from colorectal cancer (CRC) patients uncovered a novel association between mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) and NK cell infiltration that influences disease progression. ACAT1, a metabolic enzyme involved in reversible conversion of acetoacetyl-CoA to two molecules of acetyl-CoA, exhibits nuclear protein acetylation activity through its translocation. Under immune stimulation, mitochondrial ACAT1 can be phosphorylated at serine 60 (S60) and enters the nucleus; however, this process is hindered in nutrient-poor tumor microenvironments. Nuclear ACAT1 directly acetylates lysine 146 of p50 (NFKB1), attenuating its DNA binding and transcriptional repression activity and thereby increasing the expression of immune-related factors, which in turn promotes NK cell recruitment and activation to suppress colorectal cancer growth. Furthermore, significant associations were found among low nuclear ACAT1 levels, decreased S60 phosphorylation, and reduced NK cell infiltration, as well as poor prognosis in CRC. Our findings reveal an unexpected function of ACAT1 as a nuclear acetyltransferase and elucidate its role in NK cell-dependent antitumor immunity through p50 acetylation.
2025-03-17 | GSE291785 | GEO
Project description:We report an in situ vaccination, adaptable to nearly any type of cancer, that combines radiotherapy targeting one tumor and intratumoral injection of this site with tumor-specific antibody and interleukin-2 (IL-2; 3xTx). In a phase I clinical trial, administration of 3xTx (with an immunocytokine fusion of tumor-specific antibody and IL-2, hu14.18-IL2) to subjects with metastatic melanoma increases peripheral CD8+ T cell effector polyfunctionality. This suggests the potential for 3xTx to promote antitumor immunity against metastatic tumors. In poorly immunogenic syngeneic murine melanoma or head and neck carcinoma models, 3xTx stimulates CD8+ T cell-mediated antitumor responses at targeted and non-targeted tumors. During 3xTx treatment, natural killer (NK) cells promote CTLA4+ regulatory T cell (Treg) apoptosis in non-targeted tumors. This is dependent on NK cell expression of CD86, which is upregulated downstream of KLRK1. NK cell depletion increases Treg infiltration, diminishing CD8+ T cell-dependent antitumor response. These findings demonstrate that NK cells sustain and propagate CD8+ T cell immunity following 3xTx
2023-12-21 | GSE209945 | GEO