Spatially Resolved Metabolomics Combined with the 3D Tumor-Immune Cell Coculture Spheroid Highlights Metabolic Alterations during Antitumor Immune Response DOI
Panpan Chen, Yuhao Han, Lei Wang

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(41), P. 15153 - 15161

Published: Oct. 6, 2023

The metabolic cross-talk between tumor and immune cells plays key roles in cell function checkpoint blockade therapy. However, the characterization of immunometabolism its spatiotemporal alterations during response a complex microenvironment is challenging. Here, 3D tumor-immune coculture spheroid model was developed to mimic interactions, combined with mass spectrometry imaging-based spatially resolved metabolomics visualize immunometabolic response. inhibition T simulated by coculturing breast spheroids Jurkat cells, reactivation can be monitored through diminishing cancer PD-L1 expressions berberine. This system enables simultaneously screening imaging discriminatory metabolites that are altered cell-mediated antitumor characterizing distributions berberine spheroids. We discovered transport catabolism glutamine were significantly reprogrammed at both metabolite enzyme levels, corresponding indispensable energy metabolism building new biomass. combination visually reveals interactions possibly helps decipher role immunotherapy.

Language: Английский

Ferroptosis, necroptosis, and pyroptosis in the tumor microenvironment: Perspectives for immunotherapy of SCLC DOI
Xing Niu, Lijie Chen, Yan Li

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 273 - 285

Published: March 12, 2022

Language: Английский

Citations

180
Lactate in the tumor microenvironment: A rising star for targeted tumor therapy DOI Creative Commons

Zhangzuo Li,

Qi Wang, Xu‐Feng Huang

et al.

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 16, 2023

Metabolic reprogramming is one of fourteen hallmarks tumor cells, among which aerobic glycolysis, often known as the “Warburg effect,” essential to fast proliferation and aggressive metastasis cells. Lactate, on other hand, a ubiquitous molecule in microenvironment (TME), generated primarily by cells undergoing glycolysis. To prevent intracellular acidification, malignant remove lactate along with H + , yet acidification TME inevitable. Not only does highly concentrated within serve substrate supply energy but it also works signal activate multiple pathways that enhance invasion, intratumoral angiogenesis, well immune escape. In this review, we aim discuss latest findings metabolism particularly capacity extracellular influence microenvironment. addition, examine current treatment techniques employing existing medications target interfere generation transport cancer therapy. New research shows targeting metabolism, lactate-regulated action are viable therapy strategies.

Language: Английский

Citations

50
Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer DOI Creative Commons
Moumita Kundu, Ramesh Butti, Venketesh K. Panda

et al.

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

Published: May 7, 2024

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer more challenging and may be unresponsive to conventional therapy. Immunotherapy crucial for treating but its resistance a major limitation. tumor microenvironment (TME) vital in modulating immunotherapy response. Various microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), are involved TME modulation cause resistance. This review highlights role stromal microenvironment, including involvement CAF-TAM interaction, alteration metabolism leading failure, other latest strategies, high throughput genomic screening, single-cell spatial omics techniques identifying immune genes regulating emphasizes therapeutic approach overcome through CAF reprogramming, TAM polarization, metabolism, alterations.

Language: Английский

Citations

48
The role of RNA methylation in tumor immunity and its potential in immunotherapy DOI Creative Commons
Yan Li,

Haoer Jin,

Qingling Li

et al.

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

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

Citations

32
Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer DOI
Ana Podolski-Renić, Ana Čipak Gašparović, Andreia Valente

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 270, P. 116363 - 116363

Published: March 29, 2024

Language: Английский

Citations

23
Invasion and metastasis in cancer: molecular insights and therapeutic targets DOI Creative Commons

Yongxing Li,

Fengshuo Liu,

Qingjin Cai

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 20, 2025

The progression of malignant tumors leads to the development secondary in various organs, including bones, brain, liver, and lungs. This metastatic process severely impacts prognosis patients, significantly affecting their quality life survival rates. Research efforts have consistently focused on intricate mechanisms underlying this corresponding clinical management strategies. Consequently, a comprehensive understanding biological foundations tumor metastasis, identification pivotal signaling pathways, systematic evaluation existing emerging therapeutic strategies are paramount enhancing overall diagnostic treatment capabilities for tumors. However, current research is primarily metastasis within specific cancer types, leaving significant gaps our complex cascade, organ-specific tropism mechanisms, targeted treatments. In study, we examine sequential processes elucidate driving organ-tropic systematically analyze tumors, those tailored organ involvement. Subsequently, synthesize most recent advances technologies challenges opportunities encountered pertaining bone metastasis. Our objective offer insights that can inform future practice crucial field.

Language: Английский

Citations

3
Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations DOI Creative Commons

Hsuan-Chia Chang,

Chung‐Ying Tsai,

Cheng-Lung Hsu

et al.

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Preclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of L-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The L-asparaginase notably immune-checkpoint blockade therapy in by strengthening CD8+T fitness. Our study shows this combination is a promising avenue for clinical application and provides further mechanistic insight into how restriction rewires metabolism.

Language: Английский

Citations

2
Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies DOI
Disha D. Shah, Mehul R. Chorawala, Neha R. Raghani

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 18, 2025

Language: Английский

Citations

2
Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application DOI Creative Commons
Fusheng Zhang, Haiyang Liu,

Meiqi Duan

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 6, 2022

Abstract The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, immunosuppression. One the most common RNA N6-methyladenosine (m 6 A) methylation, widely involved regulation physiological pathological processes, including development. Compelling evidence indicates that m A methylation regulates transcription protein expression through shearing, export, translation, processing, thereby participating dynamic evolution TME. Specifically, methylation-mediated adaptation to phenotypic shift immune cells synergistically promote formation an immunosuppressive supports proliferation metastasis. In this review, we have focused on involvement tumor-adaptive described detailed linking change cell biological functions. view collective data, advocate treating as complete ecosystem components crosstalk with each other achieve adaptive changes. Finally, describe potential utility methylation-targeted therapies immunotherapy clinical applications challenges faced, aim advancing research.

Language: Английский

Citations

60
Echinacea purpurea-derived homogeneous polysaccharide exerts anti-tumor efficacy via facilitating M1 macrophage polarization DOI Creative Commons
Wenkai Ren, Junfeng Ban, Yaoyao Xia

et al.

The Innovation, Journal Year: 2023, Volume and Issue: 4(2), P. 100391 - 100391

Published: Feb. 9, 2023

Echinacea purpurea modulates tumor progression, but the underlying mechanism is poorly defined. We isolated and purified a novel homogeneous polysaccharide from E. (EPPA), which was shown to be an arabinogalactan with mean molecular mass (Mr) of 3.8 × 104 Da α- (1 → 5) -L-Arabinan as backbone α-L-Araf-(1→, →6)-β-D-Galp-(1→, →4)-α-D-GalpA-(1→ side chains. Interestingly, oral administration EPPA suppresses progression in vivo shapes immune cell profile (e.g., facilitating M1 macrophages) microenvironment by single-cell RNA sequencing (scRNA-seq) analysis. More importantly, activates inflammasome through phagocytosis-dependent rewires transcriptomic metabolic profile, thereby potentiating macrophage polarization. Collectively, we propose that supplementation could function adjuvant therapeutic strategy for suppression.

Language: Английский

Citations

40