An integrated toolbox to profile macrophage immunometabolism DOI Creative Commons
Sanne G. S. Verberk, Kyra E. de Goede, Friederike Gorki

et al.

Cell Reports Methods, Journal Year: 2022, Volume and Issue: 2(4), P. 100192 - 100192

Published: March 28, 2022

Macrophages are dynamic immune cells that can adopt several activation states. Fundamental to these functional states is the regulation of cellular metabolic processes. Especially in mice, alterations underlying pro-inflammatory or homeostatic phenotypes have been assessed using various techniques. However, researchers new field may encounter ambiguity choosing which combination techniques best suited profile immunometabolism. To address this need, we developed a toolbox assess metabolism semi-high-throughput 96-well-plate-based format. Application activated mouse and human macrophages enables fast pre-screening robust measurement extracellular fluxes, mitochondrial mass membrane potential, glucose lipid uptake. Moreover, propose an application SCENITH technology for

Language: Английский

Lipid metabolism in T cell signaling and function DOI
Seon Ah Lim, Wei Su, Nicole M. Chapman

et al.

Nature Chemical Biology, Journal Year: 2022, Volume and Issue: 18(5), P. 470 - 481

Published: April 28, 2022

Language: Английский

Citations

144

Discovering dominant tumor immune archetypes in a pan-cancer census DOI Creative Commons
Alexis J. Combes, Bushra Samad, Jessica Tsui

et al.

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 184 - 203.e19

Published: Dec. 27, 2021

Language: Английский

Citations

115

γδ T cells: origin and fate, subsets, diseases and immunotherapy DOI Creative Commons
Yi Hu,

Qinglin Hu,

Yongsheng Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Language: Английский

Citations

111

To metabolomics and beyond: a technological portfolio to investigate cancer metabolism DOI Creative Commons
Federica Danzi,

Raffaella Pacchiana,

Andrea Mafficini

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 22, 2023

Abstract Tumour cells have exquisite flexibility in reprogramming their metabolism order to support tumour initiation, progression, metastasis and resistance therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic redox status sustain increased energetic demand cells. Over last decades, cancer field has seen an explosion new biochemical technologies giving more tools than ever before navigate this complexity. Within cell or tissue, metabolites constitute direct signature molecular phenotype thus profiling concrete clinical applications oncology. Metabolomics fluxomics, are key technological approaches that mainly revolutionized enabling researchers both qualitative mechanistic model cancer. Furthermore, upgrade from bulk single-cell analysis provided unprecedented opportunity investigate biology at cellular resolution allowing depth quantitative complex heterogenous diseases. More recently, advent functional genomic screening allowed identification pathways, processes, biomarkers novel therapeutic targets concert with other allow patient stratification treatment regimens. This review is intended be guide for metabolism, highlighting current emerging technologies, emphasizing advantages, disadvantages potential leading development innovative anti-cancer

Language: Английский

Citations

108

TCR-Vγδ usage distinguishes protumor from antitumor intestinal γδ T cell subsets DOI
Bernardo Sgarbi Reis,

Patrick W. Darcy,

Iasha Z. Khan

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6603), P. 276 - 284

Published: July 14, 2022

γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but they also constitute major lymphocyte population infiltrating colorectal cancers (CRCs); however, their temporal contribution to CRC development or progression remains unclear. Using human samples and murine models, we found that most in premalignant nontumor colons exhibit cytotoxic markers, whereas tumor-infiltrating express protumorigenic profile. These contrasting cell profiles were associated with distinct receptor (TCR)-Vγδ gene usage both humans mice. Longitudinal intersectional genetics antibody-dependent strategies targeting enriched the epithelium steady state led heightened tumor development, subsets accumulate during resulted reduced growth. Our results uncover pro- antitumor roles for subsets.

Language: Английский

Citations

90

Diet, lipids, and antitumor immunity DOI Creative Commons
Hannah Prendeville, Lydia Lynch

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(3), P. 432 - 444

Published: Jan. 5, 2022

Tumour growth and dissemination is largely dependent on nutrient availability. It has recently emerged that the tumour microenvironment rich in a diverse array of lipids increase abundance with progression play role promoting metastasis. Here, we describe pro-tumorigenic roles lipid uptake, metabolism synthesis detail therapeutic potential targeting cancer. Additionally, highlight new insights into distinct immunosuppressive effects microenvironment. Lipids threaten an anti-tumour environment whereby metabolic adaptation to linked immune dysfunction. Finally, differential commondietary cancer which may uncover for specific dietary regimens association traditional therapies. Understanding relationship between lipids, tumour, cells important context obesity reveal possibility harness diet treatment cancers.

Language: Английский

Citations

78

Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment DOI Creative Commons
Zhifei Gao, Yifeng Bai, Anqi Lin

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 15, 2023

Abstract As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy recent years. They extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious tumor patients, become pioneer drugs since they were incorporated into practice. In addition, that infiltrated tissues found to be state exhaustion or anergy, there is upregulation many immune checkpoints (ICs) on their surface, suggesting similar ability respond ICIs as traditional effector T cells. Studies shown targeting ICs can reverse dysfunctional microenvironment (TME) exert effects by improving γδT-cell proliferation activation enhancing cytotoxicity. Clarification functional TME mechanisms underlying interaction with will solidify combined good treatment option.

Language: Английский

Citations

73

Obesity-induced dysregulation of skin-resident PPARγ+ Treg cells promotes IL-17A-mediated psoriatic inflammation DOI Creative Commons
Pulavendran Sivasami, Cody Elkins, Pamela P. Diaz-Saldana

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(8), P. 1844 - 1861.e6

Published: July 20, 2023

Language: Английский

Citations

49

Roles of exosomes in immunotherapy for solid cancers DOI Creative Commons
C. Lyu, Haifeng Sun, Zhenqiang Sun

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 1, 2024

Abstract Although immunotherapy has made breakthrough progress, its efficacy in solid tumours remains unsatisfactory. Exosomes are the main type of extracellular vesicles that can deliver various intracellular molecules to adjacent or distant cells and organs, mediating biological functions. Studies have found exosomes both activate immune system inhibit system. The antigen major histocompatibility complex (MHC) carried make it possible develop them as anticancer vaccines. derived from blood, urine, saliva cerebrospinal fluid be used ideal biomarkers cancer diagnosis prognosis. In recent years, exosome-based therapy great progress fields drug transportation immunotherapy. Here, we review composition sources microenvironment further elaborate on potential mechanisms pathways by which influence for cancers. Moreover, summarize clinical application prospects engineered exosome vaccines Eventually, these findings may open up avenues determining diagnosis, treatment, prognosis

Language: Английский

Citations

39

MMR vaccination induces trained immunity via functional and metabolic reprogramming of γδ T cells DOI Creative Commons
Rutger J. Röring, Priya A. Debisarun, Javier Botey-Bataller

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(7)

Published: Jan. 30, 2024

The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In randomized placebo-controlled trial, 39 healthy adults received either or placebo. By using single-cell RNA-sequencing, we found caused transcriptomic CD14-positive monocytes NK most profoundly γδ T cells. Monocyte function was not altered by vaccination. contrast, of cells markedly enhanced vaccination, with higher production TNF IFNγ, as well upregulation cellular metabolic pathways. conclusion, describe immunity program characterized modulation cell induced

Language: Английский

Citations

19