Approaches to investigate tissue-resident innate lymphocytes metabolism at the single-cell level DOI Creative Commons

Carrie Corkish,

Cristhiane Fávero de Aguiar, David K. Finlay

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 30, 2024

Abstract Tissue-resident innate immune cells have important functions in both homeostasis and pathological states. Despite advances the field, analyzing metabolism of tissue-resident lymphocytes is still challenging. The small number such as ILC, NK, iNKT γδ T poses additional obstacles their metabolic studies. In this review, we summarize current understanding lymphocyte discuss potential pitfalls associated with methodology relying predominantly on vitro cultured or bulk-level comparison. Meanwhile, also advocate for development adoption single-cell assays to accurately profile directly ex vivo.

Язык: Английский

ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses DOI Creative Commons
Irem Kaymak, McLane J. Watson, Brandon M. Oswald

и другие.

The Journal of Experimental Medicine, Год журнала: 2024, Номер 221(9)

Опубликована: Июль 4, 2024

Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an metabolic node CD8 function in vivo. We show that responses to infection depend on derived from citrate via the enzyme ATP lyase (ACLY). However, ablation ACLY triggers alternative, acetate-dependent pathway mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2). Mechanistically, acetate fuels both TCA cycle and production, impacting effector responses, histone acetylation, chromatin accessibility at gene loci. When functional, ACSS2 not required, suggesting obligate substrate function. loss renders cells dependent (via ACSS2) maintain Together, coordinate

Язык: Английский

Процитировано

8
La dolce vita: fueling chimeric antigen receptor (CAR) T cells with Glut1 to improve therapeutic efficacy DOI Open Access
Karen Slattery, David K. Finlay, Phillip K. Darcy

и другие.

Immunometabolism, Год журнала: 2025, Номер 7(1), С. e00055 - e00055

Опубликована: Янв. 1, 2025

The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment hematological cancers has marked a new era in cancer care, with seven products being FDA approved since 2017. However, challenges remain, and while profound effects are observed initially myeloma, majority patients relapse, which is concomitant poor CAR persistence. Similarly, efficacy therapy limited solid tumors, largely due to tumor heterogeneity, immune evasion mechanisms, infiltration In this recent study, Guerrero et al endeavor improve human cells by overexpressing glucose transporter GLUT1 show that have improved capacity persist control burden vivo.

Язык: Английский

Процитировано

0
Emerging insights into the impact of systemic metabolic changes on tumor-immune interactions DOI
Andrea L Cote, Chad J. Munger, Alison E. Ringel

и другие.

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115234 - 115234

Опубликована: Янв. 23, 2025

Язык: Английский

Процитировано

0
Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects DOI Creative Commons
Zhixun Guo, Jiali Ma, Jinqiu Zhang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 24, 2025

Background Esophageal cancer (EC) is the seventh-most prevalent worldwide and a significant contributor to cancer-related mortality. Metabolic reprogramming in tumors frequently coincides with aberrant immune function alterations, extensive research has demonstrated that perturbations energy metabolism within tumor microenvironment influence occurrence progression of esophageal cancer. Current treatment modalities for primarily include encompass chemotherapy limited array targeted therapies, which are hampered by toxicity drug resistance issues. Immunotherapy, particularly checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway, exhibited promising results; however, substantial proportion patients remain unresponsive. The optimization these immunotherapies requires further investigation. Mounting evidence underscores importance modulating metabolic traits (TME) augment anti-tumor immunotherapy. Methods We selected relevant studies on cells based our searches MEDLINE PubMed, focusing screening experimental articles reviews related glucose metabolism, amino acid lipid as well their interactions cells, published last five years. analyzed discussed studies, while also expressing own insights opinions. Results A total 137 were included review: 21 focused cancer, 33 delved into immunology, 30 introduced responses, 17 relationship between both cells. Conclusion This article delves alterations TME EC, systematically synthesizes characteristics TME, dissects consolidates harnesses pertinent immunotherapy targets, goal enhancing thereby offering development novel therapeutic strategies.

Язык: Английский

Процитировано

0
Biosynthetic plasticity enables CD8+ T cell functional resilience under nutrient stress DOI Creative Commons
Michael Scaglione, Montana Knight, Krittin Trihemasava

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Summary / Abstract To maintain lineage-specific functions, cells must acquire and allocate nutrients across diverse cellular processes, even in metabolically-dysregulated environments. The mechanisms allowing CD8+ T to immune function perturbed environments are poorly understood. We find that adapt nutrient stresses over time, reconfiguring gene-regulatory metabolic networks license functional recovery. Under acute stress, reorient translational programming, limiting demand while prioritizing stress-sensitive transcriptional responses. Within these responses, the transcription factors ATF4 CEBPG jointly establish an adaptive program, promoting amino acid synthesis uptake maintaining mitochondrial anaplerosis. Despite diminished energetic capacity under environmental this program prevents failure of central carbon metabolism, mitigating stress amplification dysfunction potentiate anti-tumor immunity. Altogether, we demonstrate biosynthetic plasticity via reprioritization confers resilience unfavorable environments, offering novel strategies enhance immunotherapies.

Язык: Английский

Процитировано

0
The tumor microenvironment is an ecosystem sustained by metabolic interactions DOI Creative Commons
Emily Kay, Sara Zanivan

Cell Reports, Год журнала: 2025, Номер 44(3), С. 115432 - 115432

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Immune suppression by human thymus-derived effector Tregs relies on glucose/lactate-fueled fatty acid synthesis DOI Creative Commons
Sander de Kivit, Mark Mensink, Sarantos Kostidis

и другие.

Cell Reports, Год журнала: 2024, Номер 43(9), С. 114681 - 114681

Опубликована: Авг. 24, 2024

Regulatory T cells (Tregs) suppress pro-inflammatory conventional cell (Tconv) responses. As lipids impact signaling and function, we compare the lipid composition of CD4

Язык: Английский

Процитировано

2
Focusing on CD8+ T-cell phenotypes: improving solid tumor therapy DOI Creative Commons

Zhouchi Yao,

Yayun Zeng,

Cheng Liu

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Сен. 28, 2024

Язык: Английский

Процитировано

2
The role of GOT1 in cancer metabolism DOI Creative Commons
Huan Peng,

Hong-tao Dou,

shu he

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Дек. 24, 2024

GOT1, a cytoplasmic glutamic oxaloacetic transaminase, plays critical role in various metabolic pathways essential for cellular homeostasis and dysregulated metabolism. Recent studies have highlighted the significant plasticity roles of GOT1 reprogramming through participating both classical non-classical glutamine metabolism, glycolytic other pathways. This review summarizes emerging insights on cancer cells emphasizes response to altered metabolism when expression is altered. We how repurpose cell intrinsic their flexibility inhibited delineate molecular mechanisms GOT1’s interaction with specific oncogenes regulators at multiple levels, including transcriptional epigenetic regulation, which govern growth These may provide new directions research novel targets treatment.

Язык: Английский

Процитировано

1
NRF2-dependent regulation of the prostacyclin receptor PTGIR drives CD8 T cell exhaustion DOI

Michael S. Dahabieh,

Lisa M. DeCamp, Brandon M. Oswald

и другие.

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

Опубликована: Июнь 28, 2024

Abstract The progressive decline of CD8 T cell effector function—also known as terminal exhaustion—is a major contributor to immune evasion in cancer. Yet, the molecular mechanisms that drive dysfunction remain poorly understood. Here, we report Kelch-like ECH-associated protein 1 (KEAP1)-Nuclear factor erythroid 2-related 2 (NRF2) signaling axis, which mediates cellular adaptations oxidative stress, directly regulates exhaustion. Transcriptional profiling dysfunctional cells from chronic infection and cancer reveals enrichment NRF2 activity terminally exhausted (Tex term ) cells. Increasing (via conditional deletion KEAP1) promotes increased glutathione production antioxidant defense yet accelerates development (PD-1 + TIM-3 response or tumor challenge. Mechanistically, identify PTGIR, receptor for circulating eicosanoid prostacyclin, an NRF2-regulated dysfunction. Silencing PTGIR expression restores anti-tumor function KEAP1-deficient Moreover, lowering both reduces exhaustion enhances responses (i.e. IFN-γ granzyme production) Together, these results establish KEAP1-NRF2 axis metabolic sensor linking stress prostacyclin checkpoint fate decisions between states. One Sentence Summary pathway is hyperactivated drives via transcriptional regulation receptor, Ptgir .

Язык: Английский

Процитировано

0