Exploring the role of metabolic pathways in TNBC immunotherapy: insights from single-cell and spatial transcriptomics

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

The article provides an overview of the current understanding interplay between metabolic pathways and immune function in context triple-negative breast cancer (TNBC). It highlights recent advancements single-cell spatial transcriptomics technologies, which have revolutionized analysis tumor heterogeneity microenvironment TNBC. review emphasizes crucial role reprogramming modulating cell function, discussing how specific pathways, such as glycolysis, lipid metabolism, amino acid can directly impact activity phenotypes various populations within TNBC microenvironment. Furthermore, explores implications these metabolic-immune interactions for efficacy checkpoint inhibitor (ICI) therapies TNBC, suggesting that strategies targeting may enhance responsiveness to ICI treatments. Finally, outlines future directions potential combination integrate modulation with immunotherapeutic approaches, offering promising avenues improving clinical outcomes patients.

Language: Английский

---

Identification of cuproptosis-related lncRNAs with the significance in prognosis and immunotherapy of oral squamous cell carcinoma

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 171, P. 108198 - 108198

Published: Feb. 21, 2024

Language: Английский

---

Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3347 - 3347

Published: March 15, 2024

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving understanding of BCa pathology and contributing to a better molecular classification subtypes. To gain further insight into profile underlying development BCa, systematic literature search was performed in PubMed until November 2023, following PRISMA guidelines. This enabled identification 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based characterize metabolite signature associated with BCa. A total 1562 metabolites were identified be altered by different types samples. Urine samples displayed higher likelihood containing that are also present bladder tumor tissue cell line cultures. The data from these comparisons suggest concentrations L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid glycoursodeoxycholic decreased content deoxycytidine, 5-aminolevulinic pantothenic should considered components metabolome signature. Overall, profiling biological metabolomics is promising approach identifying potential biomarkers for early diagnosis However, future needed understand its significance context validate clinical application.

Language: Английский

---

Immunometabolism in the tumor microenvironment and its related research progress

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 31, 2022

The tumor immune microenvironment has been a research hot spot in recent years. cytokines and metabolites the can promote occurrence development of various ways help cells get rid surveillance system complete escape. Many studies have shown that existence is an important reason for failure immunotherapy. impact on systematic study. current this aspect may be only tip iceberg, relative lack integrity, related to heterogeneity tumor. This review mainly discusses status glucose metabolism lipid microenvironment, including phenotype microenvironment; effects these metabolic methods their three Impact: regulatory T (Tregs), tumor-associated macrophages (TAM), natural killer (NK cells); targeted At end article,the potential relationship between Ferroptosis years also briefly described.

Language: Английский

---

Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-L1 treatment

Cancer Drug Resistance, Journal Year: 2023, Volume and Issue: 6(3), P. 611 - 41

Published: Sept. 4, 2023

The development of immune checkpoint blockade (ICB) therapies has been instrumental in advancing the field immunotherapy. Despite prominence these treatments, many patients exhibit primary or acquired resistance, rendering them ineffective. For example, anti-PD-1/PD-L1 treatments are widely utilized across a range cancer indications, but response rate is only 10%-30%. As such, it necessary for researchers to identify targets and develop drugs that can be used combination with existing ICB overcome resistance. intersection cancer, metabolism, system gained considerable traction recent years as way comprehensively study mechanisms drive oncogenesis, evasion, immunotherapy result, new research continuously emerging support targeting metabolic pathways an adjuvant boost patient Due plethora studies highlighting this notion, review will integrate relevant articles demonstrate how tumor-derived alterations energy, amino acid, lipid metabolism dysregulate anti-tumor responses resistance therapy.

Language: Английский

---

Glioblastoma cells secrete ICAM1 via FASN signaling to promote glioma-associated macrophage infiltration

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111823 - 111823

Published: April 1, 2025

Language: Английский

---

Integrative multi-omics study identifies sex-specific molecular signatures and immune modulation in bladder cancer

Frontiers in Bioinformatics, Journal Year: 2025, Volume and Issue: 5

Published: May 19, 2025

Introduction Bladder cancer shows distinct sex-related patterns, with male patients experiencing significantly higher incidence and female facing poorer survival outcomes. This study aimed to investigate the biological mechanisms underlying these differences using integrative multi-omics analysis. Methods We analyzed bladder data from TCGA GTEx, including genomic mutations, gene expression profiles, clinical information. performed protein-protein interaction analysis, pathway enrichment, immune cell correlation. Results identified androgen receptor (AR)-related pathways as uniquely enriched in male-specific hub genes, while Wnt signaling was female-specific genes. In total, 14 genes showed significant sex-biased associations, known markers—DLGAP5, SOX2, LAMA2, COL5A2—and novel ones such ERCC5, NID1, ANK2, others. For females, three genes—RAD51C, COL22A1, COL5A2—were associations. Additionally, four genes—DAXX, IKBKB, PDGFRA, PPARG—were immune-related sex-differential correlations infiltration, of them associated AR regulation. Discussion These findings provide new insights into molecular basis sex could pave way for more personalized effective therapeutic strategies tailored patients.

Language: Английский

---

Abnormal changes in metabolites caused by m6A methylation modification: The leading factors that induce the formation of immunosuppressive tumor microenvironment and their promising potential for clinical application

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: April 1, 2024

N6-methyladenosine (m6A) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within tumor microenvironment (TME) and are essential for meeting demands cellular growth maintaining tissue homeostasis, enabling cells to adapt specific conditions TME. An increasing number research studies focused on role m6A glucose, amino acid lipid metabolism, revealing their capacity induce aberrant changes metabolite levels. These may turn trigger oncogenic signaling pathways, leading substantial alterations Notably, certain metabolites, including lactate, succinate, fumarate, 2-hydroxyglutarate (2-HG), glutamate, glutamine, methionine, S-adenosylmethionine, fatty acids cholesterol, exhibit pronounced deviations from normal not only foster tumorigenesis, proliferation angiogenesis but also give rise an immunosuppressive TME, thereby facilitating immune evasion by tumor. The primary objective this review is comprehensively discuss regulatory aforementioned metabolites potential impact development TME through alterations. This aims elaborate intricate networks governed m6A-metabolite-TME axis underscores its pivotal progression. Furthermore, we delve into implications novel targeted therapeutic strategies cancer research.

Language: Английский

---

Obesity enhances the response to neoadjuvant anti‐PD1 therapy in oral tongue squamous cell carcinoma

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(12)

Published: June 1, 2024

Abstract Objectives Previous studies have demonstrated that obesity may impact the efficacy of anti‐PD1 therapy, but underlying mechanism remains unclear. In this study, our objective was to determine prognostic value in patients with oral tongue squamous cell carcinoma (OTSCC) treated pembrolizumab and establish a subtype based on fatty acid metabolism‐related genes (FAMRGs) for immunotherapy. Materials Methods We enrolled total 56 OTSCC who underwent neoadjuvant therapy. Univariate multivariate Cox regression analyses, Kaplan–Meier survival analysis, immunohistochemistry staining were performed. Additionally, we acquired gene expression profiles pan‐cancer samples conducted GSEA KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA TIMER utilized construct FAMRGs subtype. Results Our findings indicate high Body Mass Index (BMI) significantly associated improved PFS (HR = 0.015; 95% CI, 0.001 0.477; p 0.015), potentially attributed increased infiltration PD1 + T cells. A 91 differentially expressed identified between response non‐response groups Of these, 6 hub (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 PSME1) found affect PD‐1 HNSCC, which Conclusion This study demonstrates serves as robust predictor undergoing Furthermore, plays pivotal role context therapy deserves further investigation.

Language: Английский

---

Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(10), P. e007567 - e007567

Published: Oct. 1, 2023

Acral melanoma (AM) has distinct characteristics as compared with cutaneous and exhibits poor response to immune checkpoint inhibitors (ICIs). Tumor-intrinsic mechanisms of exclusion have been identified in many cancers but less studied AM. We characterized clinically annotated tumors from patients diagnosed AM at our institution correlation ICI using whole transcriptome RNAseq, exome sequencing, CD8 immunohistochemistry, multispectral immunofluorescence imaging. A defined interferon-γ-associated T cell-inflamed gene signature was used categorize into non-T phenotypes. In combination two published studies, we systematically assessed the landscape detected differential expression pathway activation a tumor microenvironment (TME). Two single-cell(sc) RNAseq cohorts 11 bulk various types were for independent validation on pathways associated lack response. total, 892 specimens included this study. 72.5% showed low signature, 23.9% total categorized phenotype. Patients CD3 + PD1 intratumoral cell density prognosis. oncogenic significantly upregulated relative TME shared across all three acral (MYC, HGF, MITF, VEGF, EGFR, SP1, ERBB2, TFEB, SREBF1, SOX2, CCND1). scRNAseq analysis revealed that cell-expressing scores higher versus high cell-infiltrated tumors. further demonstrated enriched non-responders responders cancers, including AM, melanoma, triple-negative breast cancer, non-small lung cancer. Pathway interferon stimulated genes, suggesting suppression antigen presentation. Across pathways, fatty acid synthase CXCL8 unifying downstream target molecules potential nodes therapeutic intervention. unique set is resistance These data may inform immunotherapy combinations immediate clinical translation.

Language: Английский

---