Multi-omics analyses were combined to construct ubiquitination-related features in colon adenocarcinoma and identify ASNS as a novel biomarker DOI Creative Commons
Zhaohui Wang, Wenbing Zhang,

Xin Yin

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 9, 2024

Background As one of the malignant tumors with highest incidence and fatality in world, colon adenocarcinoma (COAD) has a very complex pathogenic mechanism, which not yet been fully elucidated. Ubiquitin can regulate cell proliferation, cycle, apoptosis, DNA damage repair, other processes by changing activity substrate proteins or causing ubiquitin-proteasome degradation. These are key links pathogenesis COAD, ubiquitin plays an important role occurrence development COAD. Methods We integrated transcriptomics, single-cell clinical omics, TCGA GEO databases COAD patient data. Cox Lasso regression was employed to assess ubiquitination genes for generating ubiquitination-related features. The aim evaluate prognostic value these features their impact on immune microenvironment. At same time, expression level model further analyzed using Finally, function ASNS, gene this trait, were detected vitro . Results In our study, based identifiable changes marker genes, feature be used classify patients Kaplan-Meier survival analysis indicated that those elevated risk scores each cohort experienced inferior outcomes. There is good validation both training queue queue. results infiltration showed rate significantly increased high-risk group. After knockdown signature, migration capacity SW620 RKO lines colony formation dramatically reduced tests. Conclusion screened constructed features, as reliable indicators ASNS identified possible biomarker

Язык: Английский

Advances in single-cell RNA sequencing and its applications in cancer research DOI Creative Commons
Dezhi Huang,

Naya Ma,

Xinlei Li

и другие.

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Авг. 24, 2023

Abstract Cancers are a group of heterogeneous diseases characterized by the acquisition functional capabilities during transition from normal to neoplastic state. Powerful experimental and computational tools can be applied elucidate mechanisms occurrence, progression, metastasis, drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect average gene expression in sample, making it difficult understand tumor heterogeneity microenvironment. The emergence development single-cell (scRNA-seq) technologies have provided opportunities subtle changes biology identifying distinct cell subpopulations, dissecting microenvironment, characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used cancer studies explore which increased understanding tumorigenesis evolution. This review summarizes basic processes their increasing applications research clinical practice.

Язык: Английский

Процитировано

89
Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy DOI Creative Commons
Jeremy Baldwin, Christoph Heuser, Tanmoy Saha

и другие.

Cell, Год журнала: 2024, Номер 187(23), С. 6614 - 6630.e21

Опубликована: Сен. 13, 2024

Язык: Английский

Процитировано

42
Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors DOI Creative Commons
Cody N. Heiser, Alan J. Simmons,

Frank Revetta

и другие.

Cell, Год журнала: 2023, Номер 186(25), С. 5620 - 5637.e16

Опубликована: Дек. 1, 2023

Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Analysis of spatial multi-omic data 31 human colorectal specimens enabled phylogeographic mapping tumor evolution that revealed individualized trajectories accompanying microenvironmental clonal alterations. Phylogeographic ordered events, classified tumors by their evolutionary dynamics, placed regions along global pseudotemporal encompassing the chromosomal instability (CIN+) hypermutated (HM) pathways. Integrated single-cell transcriptomic recurring epithelial programs infiltrating immune states pseudotime. We discovered an exclusion signature (IEX), consisting extracellular matrix regulators DDR1, TGFBI, PAK4, DPEP1, charts with CIN+ progression, is associated reduced cytotoxic cell infiltration, shows prognostic value in independent cohorts. This atlas provides insights into tumor-microenvironment co-evolution, serving as a resource for stratification targeted treatments.

Язык: Английский

Процитировано

43
Exploiting pancreatic cancer metabolism: challenges and opportunities DOI Creative Commons
Maria Chiara De Santis, Bruno Bockorny, Emilio Hirsch

и другие.

Trends in Molecular Medicine, Год журнала: 2024, Номер 30(6), С. 592 - 604

Опубликована: Апрель 10, 2024

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as key factor in tumor initiation, progression, therapy resistance has gained prominence. In this review we the impact changes interplay among stromal, immune, cells, glutamine branched-chain amino acids (BCAAs) emerge pivotal players modulating immune cell functions growth. We also discuss ongoing clinical trials that explore modulation PDAC, targeting mitochondrial metabolism, asparagine addiction, autophagy inhibition. Overcoming challenges understanding nutrient effects immune-stromal-tumor interactions holds promise innovative therapeutic strategies.

Язык: Английский

Процитировано

18
ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition DOI Creative Commons

Ziqi Zou,

Qian Cheng,

Jiajie Zhou

и другие.

Cell Reports, Год журнала: 2024, Номер 43(4), С. 113995 - 113995

Опубликована: Март 23, 2024

The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how levels fluctuate TME to shape fates. Here, we find that 20-μM low condition, representing found plasma of patients with cancers, confers Treg-like immunosuppressive capacities upon activated cells. In vivo mouse models and human single-cell RNA-sequencing datasets reveal positive correlations between condition intratumoral Treg accumulation. Mechanistically, arginine-activated cells engage transcriptional reprogramming, using ATF4-SLC7A11-GSH axis, preserve their suppressive function. These findings improve our understanding role biology potential applications for immunotherapy strategies.

Язык: Английский

Процитировано

17
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

и другие.

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

Процитировано

2
Immunotherapy: an emerging modality to checkmate brain metastasis DOI Creative Commons

Aatiya Ahmad,

Parvez Κhan, Asad Rehman

и другие.

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Июль 15, 2023

Abstract The diagnosis of brain metastasis (BrM) has historically been a dooming that is nothing less than death sentence, with few treatment options for palliation or prolonging life. Among the available, radiotherapy (RT) and surgical resection have backbone therapy. Within past couple years, immunotherapy (IT), alone in combination traditional treatments, emerged as reckoning force to combat spread BrM shrink tumor burden. This review compiles recent reports describing potential role IT various cancers. It also examines impact microenvironment on regulating cancer can play mitigating spread. Lastly, this focuses future new clinical trials pushing boundaries BrM.

Язык: Английский

Процитировано

23
The High-Affinity IL-2 Receptor Affects White Matter Damage after Cerebral Ischemia by Regulating CD8 + T Lymphocyte Differentiation DOI

Yuqian Li,

Qian Jiang,

Xiaokun Geng

и другие.

Journal of Neuroimmune Pharmacology, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 16, 2025

Язык: Английский

Процитировано

1
Unlocking the potential of T‐cell metabolism reprogramming: Advancing single‐cell approaches for precision immunotherapy in tumour immunity DOI Creative Commons
Lihaoyun Huang, Haitao Li, Cangang Zhang

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(3)

Опубликована: Март 1, 2024

Abstract As single‐cell RNA sequencing enables the detailed clustering of T‐cell subpopulations and facilitates analysis metabolic states metabolite dynamics, it has gained prominence as preferred tool for understanding heterogeneous cellular metabolism. Furthermore, synergistic or inhibitory effects various pathways within T cells in tumour microenvironment are coordinated, increased activity specific generally corresponds to functional activity, leading diverse behaviours related immune cells, which shows potential tumour‐specific induce persistent responses. A holistic how heterogeneity governs function subsets is key obtaining field‐level insights into immunometabolism. Therefore, exploring mechanisms underlying interplay between metabolism functions will pave way precise immunotherapy approaches future, empower us explore new methods combating tumours with enhanced efficacy.

Язык: Английский

Процитировано

6
Asparagine availability controls germinal center B cell homeostasis DOI
Yavuz F. Yazicioglu,

Eros Marin,

Hana F. Andrew

и другие.

Science Immunology, Год журнала: 2024, Номер 9(102)

Опубликована: Дек. 13, 2024

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these processes are poorly understood. By integrating metabolomic and transcriptomic profiling GC cells, we identified that asparagine (Asn) metabolism was highly up-regulated essential for cell function. Asparagine synthetase (ASNS) after activation through the integrated stress response sensor GCN2. Conditional deletion

Язык: Английский

Процитировано

4