Metabolic adaptation of ovarian tumors in patients treated with an IDO1 inhibitor constrains antitumor immune responses DOI
Kunle Odunsi, Feng Qian,

Amit A. Lugade

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(636)

Published: March 16, 2022

To uncover underlying mechanisms associated with failure of indoleamine 2,3-dioxygenase 1 (IDO1) blockade in clinical trials, we conducted a pilot, window-of-opportunity study 17 patients newly diagnosed advanced high-grade serous ovarian cancer before their standard tumor debulking surgery. Patients were treated the IDO1 inhibitor epacadostat, and immunologic, transcriptomic, metabolomic characterization microenvironment was undertaken baseline posttreatment biopsies. inhibition resulted efficient kynurenine pathway tryptophan degradation accompanied by metabolic adaptation that shunted catabolism toward serotonin pathway. This elevated nicotinamide adenine dinucleotide (NAD + ), which reduced T cell proliferation function. Because NAD metabolites could be ligands for purinergic receptors, investigated impact blocking receptors presence or absence on function our mouse model. We demonstrated A2a A2b receptor antagonists, SCH58261 PSB1115, respectively, rescued -mediated suppression Combining A2a/A2b improved survival boosted antitumor immune signature mice overexpressing cancer. These findings elucidate downstream adaptive consequences cancers may undermine responses microenvironment.

Language: Английский

Tryptophan Metabolism and Gut Microbiota: A Novel Regulatory Axis Integrating the Microbiome, Immunity, and Cancer DOI Creative Commons

Yingjian Hou,

Jing Li,

Shuhuan Ying

et al.

Metabolites, Journal Year: 2023, Volume and Issue: 13(11), P. 1166 - 1166

Published: Nov. 20, 2023

Tryptophan metabolism and gut microbiota form an integrated regulatory axis that impacts immunity, metabolism, cancer. This review consolidated current knowledge on the bidirectional interactions between microbial tryptophan processing host. We focused how microbiome controls breakdown via indole, kynurenine, serotonin pathways. Dysbiosis of induces disruptions in catabolism which contribute to disorders like inflammatory conditions, neuropsychiatric diseases, metabolic syndromes, These affect immune homeostasis, neurotransmission, gut-brain communication. Elucidating mechanisms modulation could enable novel therapeutic approaches psychobiotics microbiome-targeted dietary interventions. Overall, further research microbiota-tryptophan has potential revolutionize personalized diagnostics treatments for improving human health.

Language: Английский

Citations

48
Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification DOI Creative Commons
Chunsheng Lin, Qianqian Tian,

Sifan Guo

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(10), P. 2198 - 2198

Published: May 8, 2024

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening treatment, insight into understanding pathology identifying potential targets. Metabolomics technology is crucial discovering targets of involved in phenotype. Mass spectrometry-based metabolomics has implemented applications various fields including target discovery, explanation mechanisms compound screening. It used to analyze the physiological or pathological states organism by investigating changes endogenous associated metabolism from complex metabolic pathways biological samples. The present review provides a critical update high-throughput functional techniques diverse applications, recommends use mass metabolite signatures that provide valuable insights We also recommend using as powerful tool patterns, efficacy evaluation herbal medicine.

Language: Английский

Citations

17
A metabolic dependency of EBV can be targeted to hinder B cell transformation DOI
Bojana Müller-Durovic, J. Jäger,

Christine Engelmann

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6704)

Published: May 23, 2024

After infection of B cells, Epstein-Barr virus (EBV) engages host pathways that mediate cell proliferation and transformation, contributing to the propensity drive immune dysregulation lymphomagenesis. We found EBV protein EBNA2 initiates nicotinamide adenine dinucleotide (NAD) de novo biosynthesis by driving expression metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in infected cells. Virus-enforced NAD production sustained mitochondrial complex I activity, match adenosine triphosphate (ATP) with bioenergetic requirements transformation. In transplant patients, IDO1 EBV-infected a serum signature increased preceded development lymphoma. humanized mice EBV, inhibition reduced both viremia Virus-orchestrated is therefore druggable vulnerability EBV-driven opening therapeutic possibilities for EBV-related diseases.

Language: Английский

Citations

17
Clinical landscape of macrophage-reprogramming cancer immunotherapies DOI Creative Commons
Jenna H. Rannikko, Maija Hollmén

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 131(4), P. 627 - 640

Published: June 3, 2024

Tumour-associated macrophages (TAMs) sustain a tumour-supporting and immunosuppressive milieu therefore aggravate cancer prognosis. To modify TAM behaviour unlock their anti-tumoural potential, novel TAM-reprogramming immunotherapies are being developed at an accelerating rate. At the same time, scientific discoveries have highlighted more sophisticated phenotypes with complex biological functions contradictory prognostic associations. understand evolving clinical landscape, we reviewed current past clinically evaluated therapeutics summarised almost 200 agents investigated in than 700 trials. Observable overall trends include high frequency of overlapping strategies against therapeutic targets, development to improve previously ineffective approaches reliance on combinatory for efficacy. However, strong anti-tumour efficacy is uncommon, which encourages re-directing efforts identifying biomarkers eligible patient populations comparing similar treatments earlier. Future endeavours will benefit from considering shortcomings treatment accommodating emerging complexity biology.

Language: Английский

Citations

17
Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: strategies and mechanisms DOI

Mu‐Yang Huang,

Xiaoming Jiang, Binglin Wang

et al.

Pharmacology & Therapeutics, Journal Year: 2020, Volume and Issue: 219, P. 107694 - 107694

Published: Sept. 25, 2020

Language: Английский

Citations

111
Nitrogen Metabolism in Cancer and Immunity DOI
Kiran Kurmi, Marcia C. Haigis

Trends in Cell Biology, Journal Year: 2020, Volume and Issue: 30(5), P. 408 - 424

Published: March 10, 2020

Language: Английский

Citations

106
The trans-omics landscape of COVID-19 DOI Creative Commons
Peng Wu, Dongsheng Chen, Wencheng Ding

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 27, 2021

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks especially in those patients without comorbidities, not fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude with selected yet symptoms ranging asymptomatic critically ill. Using integrative analysis genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, report trans-omics landscape COVID-19. Our analyses find neutrophils heterogeneity between ill patients. Meanwhile, over-activation, arginine depletion tryptophan metabolites accumulation correlate T cell dysfunction critical multi-omics data characterization peripheral may thus help provide clues regarding pathophysiology potential therapeutic strategies

Language: Английский

Citations

103
Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy DOI
Yixuan Guo, Yu Liu, Wei Wu

et al.

Biomaterials, Journal Year: 2021, Volume and Issue: 276, P. 121018 - 121018

Published: July 12, 2021

Language: Английский

Citations

95
Gut‐liver axis‐mediated mechanism of liver cancer: A special focus on the role of gut microbiota DOI Creative Commons
Naoko Ohtani, Eiji Hara

Cancer Science, Journal Year: 2021, Volume and Issue: 112(11), P. 4433 - 4443

Published: Sept. 17, 2021

Gut microbiota and the mammalian host share a symbiotic relationship, in which provides suitable ecosystem for gut bacteria to digest indigestible nutrients produce useful metabolites. Although primarily reside influence intestine, they also regulate liver function via absorption subsequent transfer of microbial components metabolites through portal vein liver. Due this transfer, may be continuously exposed gut-derived components. For example, short-chain fatty acids (SCFA) produced by microbiota, fermentation dietary fiber, can suppress inflammation regulatory T cell induction SCFA-induced epigenetic mechanisms. Additionally, secondary bile (BA), such as deoxycholic acid, 7α-dehydroxylation primary BAs, are thought induce DNA damage contribute remodeling tumor microenvironments. Other substances that include lipopolysaccharides (components outer membrane gram-negative bacteria) lipoteichoic acid (cell wall component Gram-positive bacteria), ligands innate immune receptors, Toll-like receptor-4, receptor-2, respectively, inflammatory signaling is elicited. In review, we focus on role microenvironment, describing anatomy gut-liver axis, metabolites, relationships exist between diseases, including cancer.

Language: Английский

Citations

84
A single-cell atlas of non-haematopoietic cells in human lymph nodes and lymphoma reveals a landscape of stromal remodelling DOI Creative Commons
Yoshiaki Abe, Mamiko Sakata‐Yanagimoto, Manabu Fujisawa

et al.

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(4), P. 565 - 578

Published: March 24, 2022

Abstract The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal and endothelial cells, in lymphomas are reported to underlie lymphomagenesis. However, our understanding lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even normal human lymph nodes (LNs). Here we constructed a single-cell transcriptome atlas more than 100,000 collected from 27 samples, LNs various nodal lymphomas, it revealed 30 distinct subclusters, some that were previously unrecognized. Notably, this was useful for comparative analyses with NHCs, which an unanticipated landscape subcluster-specific changes gene expression interaction malignant follicular NHCs. This facilitates remodelling highlights potential clinical biomarkers. Our study largely updates taxonomy analysis disease status, provides rich resource deeper insights into LN biology advance management therapy.

Language: Английский

Citations

65