Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies DOI Creative Commons
Siwei Wang, Qin Lu, Furong Liu

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 7, 2025

The cGAS-STING signaling pathway serves as a critical link between DNA sensing and innate immunity, has tremendous potential to improve anti-tumor immunity by generating type I interferons. However, STING agonists have shown decreasing biotherapeutic efficacy in clinical trials. Tumor metabolism, characterized aberrant nutrient utilization energy production, is fundamental hallmark of tumorigenesis. And modulating metabolic pathways tumor cells been discovered therapeutic strategy for tumors. As research concerning progressed, emerging evidence highlights its role reprogramming, independent immune function, indicating targets activation cancers. In this review, we delve into the interplay multiple pathways. We also synthesize current knowledge on antitumor functions STING, within microenvironment (TME) that could be exploited activation. This review necessity future dissect complex interactions with various cancer types, emphasizing personalized strategies based profiling.

Language: Английский

Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance DOI Open Access

C. Raman Suri,

Babita Pande,

Lakkakula Suhasini Sahithi

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.

Language: Английский

Citations

1
Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance DOI Creative Commons
Heng Lin,

Kole Tison,

Yuheng Du

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(12), P. 2032 - 2044.e6

Published: Nov. 7, 2024

Immune checkpoint blockade (ICB) triggers tumor ferroptosis. However, most patients are unresponsive to ICB. Tumors might evade ferroptosis in the microenvironment (TME). Here, we discover SLC13A3 is an itaconate transporter cells and endows resistance, diminishing immunity ICB efficacy. Mechanistically, uptake via from tumor-associated macrophages (TAMs), thereby activating NRF2-SLC7A11 pathway escaping immune-mediated Structural modeling molecular docking analysis identify a functional inhibitor for (SLC13A3i). Deletion of ACOD1 (an essential enzyme synthesis) macrophages, genetic ablation tumors, or treatment with SLC13A3i sensitize tumors ferroptosis, curb progression, bolster effectiveness. Thus, interplay between TAMs SLC13A3-itaconate-NRF2-SLC7A11 axis as previously unknown immune resistant mechanism TME promising immunometabolic target treating

Language: Английский

Citations

8
Methyltransferase Setd2 prevents T cell–mediated autoimmune diseases via phospholipid remodeling DOI
Yali Chen, Kun Chen, Ha Zhu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(8)

Published: Feb. 15, 2024

Coordinated metabolic reprogramming and epigenetic remodeling are critical for modulating T cell function differentiation. However, how the modification controls Th17/Treg balance via remains obscure. Here, we find that Setd2, a histone H3K36 trimethyltransferase, suppresses Th17 development but promotes iTreg polarization phospholipid remodeling. Mechanistically, Setd2 up-regulates transcriptional expression of lysophosphatidylcholine acyltransferase 4 (Lpcat4) directly catalyzing H3K36me3

Language: Английский

Citations

7
Nanotechnology-based in situ cancer vaccines: Mechanisms, design, and recent advances DOI

Gaoli Niu,

Hong Wang, Yanhong Zhai

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 56, P. 102286 - 102286

Published: May 6, 2024

Language: Английский

Citations

7
Size-switchable and dual-targeting nanomedicine for cancer chemoimmunotherapy by potentiating deep tumor penetration and antitumor immunity DOI
Lu Tang, Yue Yin, Ziyao Zhang

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 493, P. 152590 - 152590

Published: May 27, 2024

Language: Английский

Citations

7
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
Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer DOI Creative Commons
Xiaojun Zhou,

Genxin Wang,

Chenhui Tian

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 12, 2024

Abstract Tumor cells reprogram their metabolism to produce specialized metabolites that both fuel own growth and license tumor immune evasion. However, the relationships between these functions remain poorly understood. Here, we report CRISPR screens in a mouse model of colo-rectal cancer (CRC) implicates dual specificity phosphatase 18 (DUSP18) establishment tumor-directed Dusp18 inhibition reduces CRC rates, which correlate with high levels CD8 + T cell activation. Mechanistically, DUSP18 dephosphorylates stabilizes USF1 bHLH-ZIP transcription factor. In turn, induces SREBF2 gene, allows accumulate cholesterol biosynthesis intermediate lanosterol release it into microenvironment (TME). There, uptake by suppresses mevalonate pathway KRAS protein prenylation function, turn inhibits activation establishes molecular basis for escape. Finally, combination an anti-PD-1 antibody Lumacaftor, FDA-approved small molecule inhibitor DUSP18, mice synergistically enhances anti-tumor immunity. Collectively, our findings support idea checkpoint metabolic blockade represents rationally-designed, mechanistically-based potential therapy CRC.

Language: Английский

Citations

6
Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma DOI Creative Commons
Jiao Wang, Chengyu Liu, Rong‐Hua Hu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 1, 2024

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% primary liver cancer. The advent immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized treatment HCC in late-stage unresectable HCC, as ICIs alone were disappointing treating HCC. In addition to altered microenvironment, abnormal lipid metabolism been extensively characterized various types Stains are known their cholesterol-lowering properties long history hypercholesterolemia reducing cardiovascular disease risk. Apart from ICI other conventional therapies, statins frequently used by advanced patients dyslipidemia, which often marked accumulation cholesterol fatty acids liver. Supported a body preclinical clinical studies, may unexpectedly enhance efficacy therapy through regulation inflammatory responses microenvironment. This review discusses changes summarizes evidence benefits stain use prospects possible mechanistic actions transforming microenvironment when immunotherapies. Consequently, statin emerge novel valuable adjuvant immunotherapies

Language: Английский

Citations

5
Targeting lipid metabolism in cancer metastasis DOI
Gloria Pascual, Blanca Majem, Salvador Aznar Benitah

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1879(1), P. 189051 - 189051

Published: Dec. 13, 2023

Language: Английский

Citations

13
Dendronized Polymer‐Derived Nanomedicines for Mitochondrial Dynamics Regulation and Immune Modulation DOI

Xingyu Hou,

Dayi Pan, Dan Zhong

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: March 13, 2024

Abstract The effects of dendron side chains in polymeric conjugates on tumor penetration and antigen presentation are systematically examined. Three polymer‐gemcitabine (Gem) (pG0‐Gem, pG1‐Gem, pG2‐Gem) designed prepared. pG2‐Gem conjugate uniquely binds to the mitochondria cells, thus regulating mitochondrial dynamics. interaction between promotes great accumulation at site, resulting pronounced antitumor an animal model. Such encouraging therapeutic can be ascribed immune modulation since MHC‐1 is significantly enhanced due fusion metabolism alteration after treatment. Crucially, drug‐free dendronized polymer, pG2, identified regulate dynamics, regulation independent conjugated Gem. Furthermore, combination with anti‐PD‐1 antibody results a remarkable clearance rate 87.5% prolonged survival over 150 days, demonstrating potential polymers as innovative nanoplatform for metabolic synergistic immunotherapy.

Language: Английский

Citations

4