Metabolic footprint and logic through the T cell life cycle DOI Creative Commons
Tingting Fan, Rushil Shah, Ruoning Wang

et al.

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 91, P. 102487 - 102487

Published: Sept. 21, 2024

A simple definition of life is a system that can self-replicate (proliferation) and self-sustain (metabolism). At the cellular level, metabolism has evolved to drive proliferation, which requires energy building blocks duplicate biomass before division. T lymphocytes (or cells) are required for adaptive immune responses, protecting us against invading malignant agents capable hyper-replication. To gain competitive advantage over these agents, activated cells their divide into two daughter in as short 2-6 hours, considered fastest cell division among all types vertebrates. Thus, primary task commit available resources hyperproliferation. Beyond that, cycle involves an ordered series fate-determining events transition between discrete states. stages not involved hyperproliferation, engage metabolic programs more flexible sustain viability maintenance sometimes fine-tuned support specific activities. Here, we focus on central carbon metabolism, most relevant proliferation. We provide examples how changes may or change fate further explore few conceptual frameworks, such flexibility, Goldilocks Principle, overflow effector-signaling metabolites, context transitions.

Language: Английский

Principles and therapeutic applications of adaptive immunity DOI Creative Commons
Hongbo Chi, Marion Pepper, Paul G. Thomas

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2052 - 2078

Published: April 1, 2024

Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense respond with targeted precision to perturbations induced pathogens tissue damage. Here, we review key principles underlying adaptive orchestrated distinct T cell B populations their extensions disease therapies. We discuss the intracellular intercellular processes shaping antigen specificity recognition in immune activation lymphocyte functions mediating effector memory responses. also describe how balance protective autoimmunity immunopathology, including during tolerance, response chronic stimulation, adaptation non-lymphoid tissues coordinating homeostasis. Finally, extracellular signals cell-intrinsic programs underpinning conclude summarizing advances vaccination engineering responses for therapeutic interventions. A deeper understanding of these holds promise uncovering new means improve human health.

Language: Английский

Citations

64
T cell dysfunction and therapeutic intervention in cancer DOI
Caitlin C. Zebley, Dietmar Zehn, Stephen Gottschalk

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(8), P. 1344 - 1354

Published: July 18, 2024

Language: Английский

Citations

23
Immunometabolism of CD8+ T cell differentiation in cancer DOI
Hao Shi, Sidi Chen, Hongbo Chi

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(7), P. 610 - 626

Published: April 30, 2024

Language: Английский

Citations

15
A KIF20A-based thermosensitive hydrogel vaccine effectively potentiates immune checkpoint blockade therapy for hepatocellular carcinoma DOI Creative Commons

Xingyang Zhao,

Feichao Xuan,

Zirong Li

et al.

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 3, 2025

Language: Английский

Citations

1
Architects of immunity: How dendritic cells shape CD8 + T cell fate in cancer DOI
Vidit Bhandarkar, Teresa Dinter, Stefani Spranger

et al.

Science Immunology, Journal Year: 2025, Volume and Issue: 10(103)

Published: Jan. 17, 2025

Immune responses against cancer are dominated by T cell exhaustion and dysfunction. Recent advances have underscored the critical role of early priming interactions in establishing fates. In this review, we explore importance dendritic (DC) signals specifying CD8+ fates cancer, drawing on insights from acute chronic viral infection models. We highlight DCs lymph nodes tumors maintaining stem-like cells, which for durable antitumor immune responses. Understanding how determined will enable rational design immunotherapies, particularly therapeutic vaccines, that can modulate DC-T to generate beneficial

Language: Английский

Citations

1
Developing T Cell Epitope-Based Vaccines Against Infection: Challenging but Worthwhile DOI Creative Commons
Xian Tang,

Wei Zhang,

Zheng Zhang

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 135 - 135

Published: Jan. 28, 2025

T cell epitope-based vaccines are designed to elicit long-lived pathogen-specific memory cells that can quickly activate protective effector functions in response subsequent infections. These have the potential provide sustained protection against mutated variants, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which increasingly capable of evading neutralizing antibodies. Recent advancements epitope discovery, receptor analysis, and bioinformatics enabled precise selection epitopes sophisticated design vaccines. This review outlines development process for We summarize current progress discovery technologies, highlighting advantages disadvantages each method. also examine optimization vaccines, particularly through tools. Additionally, we discuss challenges validating accurate processing presentation individual establishing suitable rodent models evaluate vaccine immunogenicity efficacy.

Language: Английский

Citations

1
Spatiotemporal metabolomic approaches to the cancer-immunity panorama: a methodological perspective DOI Creative Commons
Yang Xiao, Yongsheng Li,

Huakan Zhao

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 18, 2024

Language: Английский

Citations

7
CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8+ T cell formation DOI Creative Commons
Jana Raynor,

Nicholas C. Collins,

Hao Shi

et al.

Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

5
Engineering bacteria for cancer immunotherapy by inhibiting IDO activity and reprogramming CD8+ T cell response DOI Creative Commons
Heng Wang, Fang Xu,

Chenlu Yao

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(52)

Published: Dec. 18, 2024

Inhibiting indoleamine 2,3 dioxygenase (IDO) for anticancer therapy has garnered significant attention in recent years. However, current IDO inhibitors face challenges which limit their clinical application. Here, we genetically engineered a high tryptophan-expressing Clostridium butyricum (L-Trp CB) strain that can colonize tumors strictly following systemic administration. We revealed butyrate produced by L-Trp CB inhibit activity, preventing tryptophan catabolism and kynurenine accumulation tumors. In addition, the large released provide discrete signals support CD8+ T cell activation energy metabolism within tumor microenvironment. observed significantly restored proportion function of cells, leading to delayed growth both mouse rabbit multiple models with limited side effects. here synthetic biology treatment strategy enhanced immunotherapy inhibiting activity reprogramming response

Language: Английский

Citations

5
Biosynthetic plasticity enables CD8+ T cell functional resilience under nutrient stress DOI Creative Commons
Michael Scaglione, Montana Knight, Krittin Trihemasava

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

0