Metabolic targeting of regulatory T cells in oral squamous cell carcinoma: new horizons in immunotherapy

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Дек. 19, 2024

Oral squamous cell carcinoma (OSCC) is a prevalent oral malignancy, which poses significant health risks with high mortality rate. Regulatory T cells (Tregs), characterized by their immunosuppressive capabilities, are intricately linked to OSCC progression and patient outcomes. The metabolic reprogramming of Tregs within the tumor microenvironment (TME) underpins function, key pathways such as tryptophan-kynurenine-aryl hydrocarbon receptor, PI3K-Akt-mTOR nucleotide metabolism significantly contributing suppressive activities. Targeting these offers novel therapeutic approach reduce Treg-mediated immunosuppression enhance anti-tumor responses. This review explores dependencies that sustain Treg function in OSCC, highlighting adaptations glycolysis, fatty acid oxidation, amino signaling pathway enable thrive challenging conditions TME. Additionally, discusses influence microbiome on evaluates potential strategies targeting pathways. Despite promising interventions, challenges selectivity, toxicity, heterogeneity, resistance mechanisms remain. concludes perspectives personalized medicine integrative approaches, emphasizing need for continued research translate findings into effective clinical applications treatment.

Язык: Английский

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Current Evidence on the Relation Between Microbiota and Oral Cancer—The Role of Fusobacterium nucleatum—A Narrative Review

Cancers, Год журнала: 2025, Номер 17(2), С. 171 - 171

Опубликована: Янв. 7, 2025

Oral squamous cell carcinoma (OSCC) is one the most prevalent head and neck cancers represents a major cause of morbidity mortality worldwide. The main established risk factors for OSCC include tobacco alcohol consumption betel quid chewing, which may contribute alone or in combination with other environmental to carcinogenesis. oral microbiota emerging as key player establishment molecular cellular mechanisms that trigger promote carcinogenesis, including cavity. Among bacterial species found microbiota, Fusobacterium nucleatum, an anaerobic bacterium commonly biofilms periodontal pathogen, has gained attention due solid evidence implicating F. nucleatum colorectal cancer (CRC). been shown induce chronic inflammation, proliferation invasion while deploying immune evasion mechanisms. These experimental findings were first obtained vitro vivo models CRC are being confirmed studies on OSCC. In this review, we summarize recent role OSCC, discuss clinical implications terms prognosis provide overview involved. Moreover, identify research questions aspects require investigations clarify We anticipate field have significant impact diagnosis, management

Язык: Английский

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Dysbiosis of Oral Microbiome: A Key Player in Oral Carcinogenesis? A Critical Review

Biomedicines, Год журнала: 2025, Номер 13(2), С. 448 - 448

Опубликована: Фев. 12, 2025

The oral cavity is known to harbor hundreds of microorganisms, belonging various genera, constituting a peculiar flora called the microbiome. change in relative distribution constituents this microbial flora, due any reason, leads dysbiosis. For centuries, dysbiosis has been linked etiopathogenesis several medical illnesses, both locally and systemically-. However, aided by recent advent bio-technological capabilities, reports have re-emerged that link carcinogenesis, numerous studies are currently exploring their association plausible mechanisms. Some proposed mechanisms dysbiosis-induced carcinogenesis (ODIC) include—a bacteria-induced chronic inflammatory state leading direct cellular damage, inflammatory-cytokine-mediated promotion proliferation invasion, release bacterial products carcinogenic, suppression local immunity alteration tumor microenvironment. actual interactions between these role not yet fully understood. This review provides comprehensive overview hypotheses implicated ODIC, along with corresponding molecular aberrations. Apart from discussing usual microbiome profile, also summarizes profiles ODIC. sheds light on potential clinical implications research prevention management cancer.

Язык: Английский

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Intratumoral Fusobacterium nucleatum is associated with better cancer-specific survival in head and neck cancer patients

Journal of Oral Microbiology, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 1, 2025

The oral microbiome, particularly Fusobacterium nucleatum (Fn), has been implicated in head and neck cancers (HNC), influencing local immunity Human Papillomavirus (HPV) status. Here, we evaluated the presence of Fn its association with HPV infection, TERT promoter (TERTp) mutations, patient outcomes. We analyzed 94 formalin-fixed paraffin-embedded (FFPE) tumor tissues from HNC patients previously for TERTp mutations. DNA was detected using droplet digital PCR (ddPCR), status determined via p16 immunohistochemistry pre-treatment samples. Associations between presence, clinicopathological features, HPV, mutation were assessed. Tumors primarily originated oropharynx (70.2%) cavity (29.8%). Tobacco alcohol use reported 87.2% 79.8% cases, respectively. present 59.6% higher prevalence oropharyngeal (62.1%) than (53.6%) tumors. No significant associations found TERTp, or However, positivity showed significantly improved cancer-specific survival (61.5% vs. 39.1%, p = 0.013), similar to HPV-positive (72.7% 42.7%, 0.014). correlates longer survival, highlighting potential as a prognostic marker.

Язык: Английский

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In vitro impact of Streptococcus mitis on the inhibition of oral cancer cell proliferation via mitotic modulation

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 15

Опубликована: Май 9, 2025

Introduction Recent studies have elucidated a potential correlation between oral carcinogenesis and the microbiome. However, few reports exist on interaction Streptococcus spp., most common microflora bacterium, cancer. In this study, we aimed to elucidate effects of spp. squamous cell carcinoma (OSCC) cells in vitro . Methods HSC-3 (tongue carcinoma) Ca9-22 (gingival were used as models OSCC cells, their responses examined after adding major species— S. mitis , sanguinis anginosus salivarius mutans —to culture medium. Cell viability was assessed using CCK-8 assay. Gene expression changes analyzed RNA sequencing RT-qPCR followed by Ontology analysis. Flow cytometry observe bacteria cycle. Results Among all species, had strongest inhibitory effect growth cells. revealed an increase number genes involved mitotic nuclear division, especially DUSP1 treated with mitis. showed that caused decreased G0/G1 phase increased G2/M phase, suggesting cycle arrest phase. Various treatments examine intact bacterial components cancer indicating involvement structural proteins. Conclusions This investigating association genus may play important role inhibition

Язык: Английский

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Evaluating the link between periodontitis and oral squamous cell carcinoma through Wnt/β-catenin pathway: a critical review

Frontiers in Oral Health, Год журнала: 2025, Номер 6

Опубликована: Май 12, 2025

Oral Squamous Cell Carcinoma (OSCC), the main form of oral cancer, is a major health problem globally that affects 400,000 people every year. It has been postulated periodontitis, chronic inflammatory disease characterized by alveolar bone resorption, an independent risk factor for OSCC. However, mechanisms underlying this link are not fully elucidated. demonstrated Wnt/β-catenin pathway key to transformation potentially malignant disorders (OPMD) towards OSCC (i.e., leukoplakia), particularly in OPMD histologically diagnosed as dysplasia. Using GEO database carcinogenesis (GSE85195), transcriptional modification 19 Wnt ligands and 4 regulatory proteins β-catenin, including E-cadherin, APC, AXIN GSK3B, during leukoplakia, early late stages OSCC, was determined. The expression these targets also assessed periodontitis (GEO GSE223924). Together, it found Wnt3, Wnt3a, Wnt5b Wnt7b concomitantly upregulated carcinogenesis. With results, information retrieved from literature, review discusses potential role molecular mechanism could interlink

Язык: Английский

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Microbiota and metabolite profiles of saliva, oral swab and cancer tissue from patients with oral squamous cell carcinoma (OSCC)

Infectious Agents and Cancer, Год журнала: 2025, Номер 20(1)

Опубликована: Май 22, 2025

Oral squamous cell carcinoma (OSCC) was the most common malignant type of head and neck (HNSCC) with a low survival rate. The microbiota in oral cavity or tumor tissues may play critical role OSCC. In this study, we characterized from cancer tissues, swabs saliva patients OSCC using 16S rRNA sequencing. We found differential profiles amounts compared adjacent as well healthy individuals. Fusobacterium nucleatum Porphyromonas endodontalis were increased patients. Prevotella melaninogenica These data suggested that varied according to different samples. Kyoto Encyclopedia Genes Genomes (KEGG) analysis indicated an important metabolic pathways interaction between cancers. Then analyzed metabolites by liquid chromatograph-mass spectrometry/mass spectrometry (LC-MS/MS) gas (GC-MS). Differential also observed It showed denticulaflavonol significantly while D-mannose decreased both Taken together, these results association microbiota/metabolites (such mannose) OSCC, which molecular mechanism need further investigated.

Язык: Английский

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Splenic volume as a predictor of survival in cancer patients treated with immune checkpoint inhibitors

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 30, 2025

Objective This investigation seeks to examine the association between spleen volume and prognosis in cancer patients undergoing immune checkpoint inhibitor (ICI) treatment. Methods We performed a retrospective analysis involving 61 diagnosed with hepatocellular carcinoma (HCC) who received ICIs at our institution. evaluated relationship baseline splenic its changes during ICI therapy concerning overall survival (OS) progression-free (PFS) using log-rank test. To identify relevant literature, we searched databases such as PubMed, EMBASE, Cochrane Library, Google Scholar up until February 20, 2024. The primary metrics assessed were hazard ratios (HR) for both OS PFS, pooled estimates corresponding 95% confidence intervals (CIs) calculated. Results Within study population, findings demonstrated significantly decreased (HR: 2.02, CI: 1.08–3.77, p = 0.027) PFS 1.84, 1.05–3.21, 0.032) HCC high volume, compared individuals lower volumes. Additionally, experienced an increase exhibited poorer 2.27, 1.17–4.41, 0.016) 2.40, 1.30–4.41, 0.005) than those whose decreased. meta-analysis results revealed that subjects higher volumes had reduced 1.74, 1.12–2.72, 0.014) 1.35, 1.15–1.58, < 0.001) counterparts Furthermore, data clearly highlighted increases faced clinical outcomes, indicated by 1.83, 1.36–2.46, 1.70, 1.28–2.25, relative decreases size. Conclusion A predictors of poor treated ICI.

Язык: Английский

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Integrative transcriptomic and single-cell analysis reveals IL27RA as a key immune regulator and therapeutic indicator in breast cancer

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Июнь 1, 2025

Язык: Английский

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Oral Pathogens’ Substantial Burden on Cancer, Cardiovascular Diseases, Alzheimer’s, Diabetes, and Other Systemic Diseases: A Public Health Crisis—A Comprehensive Review

Pathogens, Год журнала: 2024, Номер 13(12), С. 1084 - 1084

Опубликована: Дек. 9, 2024

This review synthesizes the findings from 252 studies to explore relationship between oral pathogens associated with periodontitis, dental caries, and systemic diseases. Individuals diseases, such as are 1.7 7.5 times (average 3.3 times) more likely develop diseases or suffer adverse pregnancy outcomes, underscoring critical connection overall health. Oral conditions periodontitis caries represent a significant health burden, affecting 26–47% of Americans. The most important pathogens, ranked by publication frequency, include herpes virus, C. albicans, S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans, intermedia, T. denticola, forsythia. disorders linked infections, similarly, cancer, respiratory, liver, bowel, fever, kidney, complications in pregnancy, cardiovascular bacteremia, diabetes, arthritis, autoimmune, bladder, dementia, lupus, Alzheimer’s Evidence supports efficacy periodontal treatments eliminating infections reducing severity substantial burden that have on Alzheimer’s, other poses public crisis.

Язык: Английский

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