Tet2 dysfunction drives myeloid neoplasm initiation and progression, yet the mechanisms underlying disease heterogeneity, age-dependent progression and immune microenvironment perturbation remain poorly understood. This study aimed to establish a hematopoietic specific Tet2 conditional knockout mouse model to elucidate these core mechanisms and recapitulate clinical features of Tet2 mutated myeloid neoplasms. We generated Mx1-Cre-mediated haematopoietic-specific Tet2 conditional knockout mice on a C57BL/6JGpt background using CRISPR-Cas9 and Cre-LoxP technologies. Haematopoietic phenotypes, pathological features and immune microenvironment dynamics were systematically characterised in 5- and 12-month-old mice, with wild-type littermates as controls. Statistical analyses were applied for intergroup comparisons of phenotypic and immunological indices. Tet2 deficiency induced myeloid neoplasms with distinct age-dependent progression. Five-month-old mice exhibited mild hematological abnormalities without overt pathology, whereas 12-month-old mice developed typical myeloid neoplasm phenotypes including pancytopenia, splenomegaly, myelodysplasia, with heterogeneous subtypes spanning myelodysplastic syndrome, myeloproliferative neoplasm and acute myeloid leukemia. These mice were also accompanied by severe immune dysregulation. Mechanistically, Tet2-deficient bone marrow established an immunosuppressive niche characterised by M2-like macrophage polarisation and a skewed CCR4 ligand profile with elevated CCL22 and diminished CCL17, which selectively recruited Foxp3⁺ regulatory T cells. Concurrently, serum cytokine profiling revealed broad immune activation spanning Th1-type, Th2-type and Th17-type responses. Male mice exhibited significantly accelerated disease progression compared with females. Tet2 deficiency drives myeloid neoplasm progression through the synergy of epigenetic dysregulation, age-related hematopoietic stem cell damage and immune microenvironment imbalance. This model recapitulates core clinical features of elderly Tet2-mutated myeloid neoplasms and provides a preclinical platform for mechanistic investigation and the development of epigenetic and immune-targeted precision therapies.
Vascular dementia (VaD), the second most common form of dementia, lacks approved disease-modifying therapies. White matter injury and demyelination are major pathological features, and oligodendrocyte-lineage damage directly limits myelin repair. M2-associated microglial responses regulate inflammation, clear cellular and myelin debris, and support oligodendrocyte differentiation and maturation. Single-cell studies, however, have exposed the limitations of the classical M1/M2 dichotomy in brain disease. In this review, M2a-, M2b-, and M2c-like states are interpreted based on experimentally specified inducing conditions and concordant molecular or functional evidence. We examine how these programs relate to oligodendrocyte injury, myelin loss, and white matter repair in VaD. with particular attention to their potentially stage-dependent contributions. Integrating these findings may inform the timing and functional focus of future interventions aimed at preserving oligodendrocyte function and promoting white matter repair in VaD.
Osteosarcoma remains a highly aggressive bone malignancy with limited therapeutic progress in metastatic and treatment-refractory disease. Beyond tumor-intrinsic drivers, the tumor microenvironment has emerged as a critical determinant of immune escape, therapeutic resistance, and poor clinical outcome. Among stromal components, cancer-associated fibroblasts (CAFs) are increasingly recognized as central regulators of extracellular matrix remodeling, immune suppression, and treatment failure; however, their specific translational relevance in osteosarcoma remains incompletely defined. In this review, we synthesize current evidence on CAF-mediated immune exclusion, immune suppression, and therapy resistance in osteosarcoma and organize the field into an evidence-stratified translational framework. We discuss how CAFs shape a treatment-refractory microenvironment through matrix deposition and stiffening, cytokine and chemokine signaling, exosome-mediated communication, and metabolic competition, while emphasizing the distinct stromal contexts of primary osteosarcoma and pulmonary metastases. We further summarize emerging CAF states and stromal-immune interaction programs identified by single-cell and spatial profiling, with emphasis on their implications for T-cell exclusion, myeloid reprogramming, chemotherapy resistance and immunotherapy response. Therapeutically, we evaluate CAF normalization, matrix-targeted intervention, local delivery strategies, and rational combination approaches, highlighting NADPH oxidase 4 inhibition, focal adhesion kinase-related stromal targeting and sequence-based chemoimmunotherapy as key translational directions that require further validation through delivery feasibility, safety assessment, and biomarker-guided patient stratification. Current evidence supports CAF-directed intervention in osteosarcoma primarily as a microenvironment-modulating and treatment-sensitizing strategy rather than as a stand-alone cytotoxic approach. Clinical translation will require osteosarcoma-specific validation in bone-relevant and immunocompetent models, multiplex CAF biomarker panels compatible with formalin-fixed, paraffin-embedded tissue, and rational treatment-sequencing strategies that integrate stromal normalization with chemotherapy, surgery, and immunotherapy.
Venous thromboembolism (VTE) remains a major cause of cardiovascular morbidity and mortality. Beyond dysregulated coagulation, accumulating evidence implicates immune and inflammatory pathways in thromboinflammatory susceptibility. However, the genetic determinants of VTE and their links to immune dysregulation remain incompletely characterized. We performed a proteome-wide two-sample Mendelian randomization analysis integrating cis-pQTL instruments and Bayesian colocalization to prioritize plasma proteins associated with VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE). Independent whole-blood transcriptomic cohorts stratified by recurrence history or recurrence-risk categories were analyzed to provide contextual information on recurrence-associated immune transcriptional states. Multi-omic analyses, including phenome-wide association analysis, single-cell transcriptomics, and experimental validation, were conducted to characterize prioritized candidates and evaluate their associations with macrophage-related thromboinflammatory phenotypes. Among 20 plasma proteins showing genome-wide significant MR associations with VTE-related outcomes, six (BCAM, VWF, GNS, ABO, TUFT1, and CHST15) demonstrated strong colocalization evidence (PP.H4 > 0.8). GNS showed directionally consistent protective associations across VTE, DVT, and PE, supported by shared genetic signals. Transcriptomic analyses demonstrated reduced GNS expression in recurrence-associated higher-risk groups. Phenome-wide analysis did not identify genome-wide significant phenotypic associations. Multi-omic analyses localized GNS expression predominantly to macrophage and fibroblast populations within thrombus tissue. Experimental validation demonstrated that bidirectional GNS modulation was associated with altered macrophage polarization, inflammatory responses, and thromboinflammatory phenotypes in vitro and in vivo. GNS emerged as a genetically prioritized and biologically plausible candidate associated with VTE-related outcomes and thromboinflammatory immune signatures. Integrative multi-omic analyses and experimental studies support a potential association between GNS, macrophage-associated immune regulation, and venous thrombosis, although the underlying mechanisms remain to be established. Further mechanistic and prospective studies are required to determine the biological and clinical relevance of GNS-associated pathways in VTE. Not applicable.
Systemic vasculitides are associated with quantitative and functional abnormalities in regulatory T cells (Tregs). Current treatments control inflammation but do not reliably re-establish antigen-specific immune tolerance, and relapse and treatment toxicity remain common. This review addresses three questions: (1) which Treg defects are supported across major vasculitis subtypes; (2) what level of evidence supports endogenous Treg expansion, polyclonal Treg transfer, and antigen-specific engineered Tregs; and (3) which target-selection, manufacturing, safety, regulatory, and implementation barriers must be resolved before chimeric antigen receptor-engineered Tregs (CAR-Tregs) can be tested clinically. We distinguish direct human vasculitis evidence from human mechanistic studies, preclinical observations in other autoimmune diseases, and untested therapeutic hypotheses. Human studies support disease-associated Treg abnormalities and provide limited early evidence for low-dose interleukin-2, whereas no published study has yet demonstrated therapeutic efficacy of CAR-Tregs in a vasculitis model or patient. Proposed targets, including activated endothelium and myeloperoxidase- or proteinase 3-related autoreactive responses, therefore remain design hypotheses that require validation. We also compare CAR-Tregs with T cell receptor-engineered Tregs, tolerogenic dendritic cells, Treg-biased interleukin-2 agents, and antigen-specific tolerizing platforms. CAR-Tregs offer a testable framework for localized immune regulation, but they are not an established treatment for vasculitis. Translation should proceed through staged target validation, disease-relevant preclinical models, standardized product-release criteria, and carefully selected early-phase cohorts with long-term safety monitoring.
Lens-related mechanisms in primary angle-closure glaucoma (PACG) remain incompletely defined. The anterior lens capsule (ALC) is a biologically active interface, but its molecular landscape in PACG is largely unknown. We aimed to define proteomic alterations in human ALCs from age-related cataract (ARC) with PACG and to evaluate whether lysosome-associated changes are implicated. We performed comparative data-independent acquisition proteomic profiling of human ALC specimens from patients with ARC alone and ARC combined with PACG. After quality control, 13 ARC and 10 PACG samples were included. Differential proteins were analyzed by enrichment, network, and receiver operating characteristic analyses. ATP6V1A was further evaluated in human ALC flat mounts, cell and animal stress models, peripheral blood mononuclear cells (PBMCs) from an additional small clinical cohort, and an exploratory UK Biobank (UKB) plasma proteomic dataset. A total of 1262 differentially expressed proteins were identified in PACG-associated ALCs. Proteins reduced in PACG were enriched for proteostasis-related chaperone and neddylation networks and converged on lysosome-related dysfunction. ATP6V1A and additional V-ATPase subunits, LAMP2, and Rag GTPase family members were coordinately decreased. Proteins increased in PACG were enriched for extracellular matrix remodeling and lipid/glycan metabolic pathways. Reduced ATP6V1A was confirmed in human ALC flat mounts, pressure-stressed lens epithelial cells, retinal stress models, and PBMCs from patients with PACG. Pharmacologic V-ATPase inhibition disrupted lysosomal homeostasis before overt loss of cell viability. UKB plasma proteomics did not recapitulate the ATP6V1A signal, but provided external support for glaucoma-associated lens-related and metabolic alterations. PACG-associated ALCs show a distinct molecular signature characterized by impaired proteostasis and ATP6V1A-associated lysosomal dysregulation. These findings identify ATP6V1A-associated lysosomal dysfunction as a candidate molecular link between elevated IOP, lens epithelial injury, and the coexistence of PACG and ARC.
Advanced therapy medicinal products (ATMPs) require robust, GMP-compliant manufacturing processes and well-defined critical quality attributes (CQAs) to ensure safety, reproducibility, and clinical applicability. Chondrocyte-based therapies represent a promising approach for cartilage repair, yet their translation into clinical practice is limited by challenges in scalable cell expansion and preservation of chondrogenic potential. This study aimed to develop a translational, GMP-compatible, risk-based framework for the expansion of human chondrocytes enriched in progenitor cells using human platelet lysate (hPL). Chondrocytes were expanded under low-density conditions in media supplemented with two different hPL formulations. Proteomic characterization of hPL batches was performed using high-resolution mass spectrometry followed by bioinformatic analyses to identify differentially abundant proteins and enriched pathways. Cellular phenotype was assessed through proliferation assays, flow cytometry, and marker expression analysis. Chondrogenic potential was evaluated using three-dimensional spheroid cultures, followed by histological and immunohistochemical analyses. A risk-based manufacturing strategy was implemented using Failure Modes and Effects Analysis (FMEA) to identify critical process parameters (CPPs) and associated risks. Proteomic analysis revealed significant differences in protein composition between hPL formulations, although both supported efficient cell expansion. Chondrocytes maintained a low immunogenic profile and expressed progenitor-associated markers, including CD146 and CD166, particularly under low-density culture conditions. Spheroid formation demonstrated preserved chondrogenic capacity, with optimal extracellular matrix deposition observed at a seeding density of 200,000 cells per well. Both hPL conditions supported type II collagen production, while differences were observed in glycosaminoglycan and type I collagen content. Risk analysis identified critical steps. Identification of targeted mitigation strategies supported the definition of CQAs linked to CPPs. This study establishes a GMP-compatible, risk-based framework for the expansion of chondrocyte-based ATMPs. The integration of biologically optimized culture conditions with a structured risk assessment approach enabled the generation of functionally competent cartilage-forming cells. These findings support further preclinical validation and contribute to the development of scalable and clinically applicable therapies for cartilage repair in patients with early osteoarthritis.
Autosomal recessive deafness type 9 (DFNB9), caused by mutations in the OTOF gene, is a key cause of congenital sensorineural hearing loss, comprising 2
Proton magnetic resonance spectroscopy (¹H MRS) enables non-invasive in vivo detection of metabolites and biochemical alterations, providing critical information for neurological disease diagnosis and metabolic monitoring. However, conventional ¹H MRS is restricted to endogenous metabolites with resonance signals clustered in the 1–5 ppm region, resulting in severe spectral overlap that fundamentally limits specific identification of target biomolecules. While reaction-responsive molecular probes are widely used in optical imaging, their integration with ¹H MRS to resolve spectral congestion remains underexplored. We develop a reaction-based chemical shift engineering strategy for ¹H MRS. Target-specific chemical reactions generate well-resolved resonance peaks beyond 5 ppm, thereby circumventing interference from endogenous metabolites and water signals. As a proof of concept, we engineered a molecular probe FS for selective detection of norepinephrine (NE), a key neurotransmitter implicated in depression. We elucidated the reaction mechanism via theoretical simulation, and validated its performance in aqueous solutions, PC12 cells, and fluoxetine-treated live rats on a 7.0 T magnetic resonance system. The probe FS undergoes specific cascade nucleophilic substitution with NE to produce 4-hydroxybutanal, which yields a characteristic aldehyde proton resonance at 9.7 ppm, fully separated from endogenous spectral signals. The probe exhibited favorable selectivity, anti-interference capacity and pH stability in vitro. Furthermore, FS successfully detected endogenous NE secretion in PC12 cells and enabled in vivo monitoring of pharmacologically elevated NE in rat brains. This work establishes a generalizable strategy to expand the metabolic detection scope of ¹H MRS via analyte-specific chemical reactions, holding significant translational potential for disease diagnosis, dynamic metabolic monitoring and preclinical drug evaluation.
With the ongoing evolution and mutation of SARS-CoV-2, current antiviral therapies face notable limitations, including emerging resistance mutations, inadequate immunomodulation, and suboptimal organ protection. This situation highlights the urgent need for novel therapeutic strategies. In this study, we evaluated the combined effects of Carrimycin (CAM) and Azvudine (FNC) in SARS-CoV-2-infected rhesus macaques (RMs), focusing on their antiviral activity, lung protection, and immunoinflammatory modulation roles. RMs were intratracheally challenged with SARS-CoV-2 and treated orally for 7 days with CAM (9 mg/kg), FNC (0.07 mg/kg), or their combination. Viral load, lung pathology, immune responses, and gut microbiota were analyzed. Both CAM and FNC monotherapies significantly inhibited SARS-CoV-2 replication, while their combination produced additive antiviral effects, reducing viral loads in throat swabs and lung tissue without significant side effects. Chest imaging and histopathological examination of lung tissues showed reduced ground-glass opacities and a mitigation of focal interstitial pneumonia with monotherapy, while the combination treatment demonstrated superior efficacy. Transcriptomic and immunofluorescence analyses of the lung indicated enhanced immunomodulation with combination therapy, including suppressed neutrophil degranulation, increased CD19⁺ B and CD3⁺ T cells, decreased CD68⁺ macrophages, and downregulation of pro-inflammatory and apoptotic markers, suggesting improved adaptive immunity and lung protection. Furthermore, CAM, but not FNC, increased beneficial short-chain fatty acid-producing gut bacteria and decreased harmful pathogens associated with COVID-19 progression. The combination of CAM and FNC showed superior efficacy in suppressing viral replication, alleviating lung injury, and correcting immune and inflammatory dysregulation, with CAM alone providing additional gut microbiota benefits. This combination represents a promising therapeutic strategy against COVID-19 and its complications.
Post-COVID-19 pulmonary fibrosis represents a significant long-term complication affecting 10–30
Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90
Glucose metabolism disorders (GMDs) are a major global health challenge, characterized by overlapping pathophysiological mechanisms. Emerging research has illuminated a reciprocal association between diabetes mellitus (DM) and neurodegenerative diseases (NDs). Specifically, hyperglycemic states intensify neuroinflammatory cascades, oxidative stress, and aberrant protein misfolding (e.g. amyloid-β aggregation), whereas neurodegenerative diseases (NDs) disrupt systemic glucose homeostasis.Thus, novel antihyperglycemic agents—including sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors—have garnered attention for their multi-target regulatory properties beyond glycemic control, demonstrating potential in mitigating neurodegenerative pathology.Preclinical studies indicate that these agents improve glycemic control and exert neuroprotective effects—including inhibition of neuroinflammation, reduction of Aβ accumulation, and enhancement of synaptic plasticity—primarily in experimental models; however, robust confirmatory data from large‑scale clinical trials in neurodegenerative diseases remain limited.This review systematically explores the multi-target regulatory abilities of novel hypoglycemic agents, including SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors, beyond hypoglycemia.We evaluate the clinical evidence supporting their therapeutic potential in glucose metabolism disorders and related neurodegenerative diseases, while addressing challenges such as unclear molecular pathways and the need for large-scale validation.Based on the existing evidence and limitations, we have proposed the key directions for future research, including clarifying the collaborative mechanism, optimizing the drug delivery system, and developing individualized treatment strategies.
Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, represent a heterogeneous group of chronic inflammatory disorders characterized by loss of self-tolerance and persistent immune activation. Growing evidence indicates that metabolic reprogramming is essential for immune cell activation and lineage commitment. Among these pathways, the glutamine-glutamate metabolic axis has emerged as an important immunometabolic regulatory network linking nutrient utilization and cellular metabolic remodeling to immune cell fate and function. Beyond supporting energy production and biosynthesis, this axis actively regulates immune cell activation, differentiation, and effector functions across multiple immune cell populations, including lymphocytes and monocytes/macrophages. Moreover, accumulating experimental and clinical evidence suggests that dysregulated glutamine-glutamate metabolism is associated with immune dysregulation and tissue injury in rheumatic diseases. This review comprehensively summarizes the roles of the glutamine-glutamate metabolic axis in regulating the fate and function of immune cells, and discusses its underlying mechanisms in the pathogenesis of rheumatic diseases. A deeper understanding of these immunometabolic mechanisms may facilitate the development of precision metabolism-based therapeutic strategies for AIRDs.
Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. Emerging evidence in cancer neuroscience suggests that tumor–nerve crosstalk can modulate tumor growth, immune remodeling, dissemination, and therapy resistance. Perineural invasion (PNI) is a hallmark of aggressive tumors and correlates with recurrence, metastasis, disease-specific death, and neuropathic pain, yet its prevalence and prognostic relevance in primary HCC remain inconsistently defined. Given the limited and heterogeneous clinical data, we synthesize available observations and propose mechanistic hypotheses for neural–tumor interactions in the hepatic niche. Potential drivers are organized into five domains—neurotrophic factors, axon guidance molecules, neurotransmitter signaling, cell adhesion molecules, and the tumor microenvironment—highlighting neuro–immune–stromal circuits that may create permissive perineural niches. We also outline experimental platforms to test these hypotheses, including co-culture systems, organoids, and microfluidic nerve-on-chip models. Targeting neural–tumor interactions may offer translational opportunities in HCC, but causality and actionable targets cannot be established without improved clinical and experimental rigor. Standardized pathological assessment and dedicated HCC-focused PNI models are needed to validate mechanisms, harmonize reporting, and enable reproducible, clinically meaningful advances.
Liver metastasis relies on the establishment of a pre-metastatic niche (PMN) before tumor cell seeding. Although low-dose irradiation can modulate local immune responses, whether prophylactic low-dose liver irradiation influences hepatic PMN formation and metastatic colonization remains unclear. We used a prophylactic low-dose liver irradiation strategy in mouse models of non-small cell lung cancer (NSCLC) liver metastasis to evaluate its effects on metastatic colonization and hepatic immune remodelling. Bulk RNA sequencing, single-cell RNA sequencing, and in vitro functional assays were performed to characterize irradiation-induced hepatocyte-monocyte signaling, and in vivo CXCL10 neutralization was used to assess its functional relevance. Prophylactic low-dose liver irradiation suppressed NSCLC liver metastasis and reshaped the hepatic immune microenvironment during PMN formation. A single 2 Gy dose showed the strongest antimetastatic effect. Mechanistically, 2 Gy irradiation induced hepatocyte-derived SAA1. SAA1 activated a TLR2–NF-κB/RELA-associated transcriptional program in inflammatory monocytes, leading to SLC7A11 upregulation, improved redox homeostasis, and increased CXCL10 secretion. SLC7A11 activity was required to sustain this chemokine-secretory phenotype. CXCL10 neutralization in vivo reduced CD8 + T-cell recruitment and attenuated the antimetastatic effect of low-dose irradiation. Prophylactic low-dose liver irradiation limits NSCLC liver metastasis and is associated with reprogramming of the PMN toward an anti-metastatic immune state. These findings link irradiation to metastatic niche immune remodeling and highlight the translational relevance of low-dose immune radiobiology in metastasis control.
Diabetic retinopathy (DR) remains a leading cause of visual impairment worldwide and is characterized by retinal microvascular dysfunction and chronic neuroinflammation. The pathogenesis of DR involves the activation of retinal microglia, which release a variety of pro-inflammatory cytokines, thereby amplifying inflammatory signaling and compromising the structural and functional integrity of the retinal vasculature. Piceatannol (PIC), a bioactive polyphenolic compound, has demonstrated potent anti-inflammatory properties and beneficial effects on vascular homeostasis. However, its role and underlying mechanisms in DR remain largely unexplored. An integrated approach combining network pharmacology and transcriptomic analyses was employed to systematically identify the potential molecular targets of PIC in DR. Molecular docking was first performed to predict the interaction between PIC and C-C motif chemokine receptor 5 (CCR5), followed by experimental validation of the binding affinity. In vitro and in vivo DR models were established using high glucose (HG)-stimulated microglia and streptozotocin-induced diabetic mice, respectively. The effects of PIC on microglial polarization, retinal vascular permeability, and inflammatory responses were subsequently evaluated. A total of 159 overlapping targets associated with both PIC and DR were identified, among which CCR5 emerged as a key target. In diabetic mice, PIC treatment restored retinal thickness, reduced the formation of acellular capillaries, and attenuated retinal vascular leakage. CCR5 was predominantly expressed in retinal microglia, whereas its ligand, CCL5, was significantly upregulated in DR. PIC inhibited microglial activation and M1 polarization, reduced the secretion of pro-inflammatory cytokines, and promoted the expression of M2-associated markers through modulation of the CCL5/CCR5/NF-κB signalling pathway. In vitro, PIC suppressed HG-induced M1 polarization of microglia and preserved the expression of endothelial tight junction proteins, including ZO-1 and Claudin-5. Furthermore, CCR5 knockdown and pharmacological activation experiments confirmed the central role of CCR5 in mediating the protective effects of PIC. PIC exerts protective effects on retinal microvascular function in DR by regulating microglial polarization. Specifically, it suppresses the pro-inflammatory M1 phenotype while promoting the anti-inflammatory M2 phenotype through inhibition of the CCL5/CCR5/NF-κB signaling pathway. Collectively, these findings suggest that PIC may represent a promising therapeutic candidate for the prevention and treatment of DR.
Conventional chimeric antigen receptor T-cell (CAR-T) manufacturing requires prolonged ex vivo processing and substantial viral input. We investigated whether brief T-cell activation combined with closed-loop microfluidic recirculation could improve low-multiplicity-of-infection (MOI) lentiviral transduction while generating functional CD19 CAR-T cells within a 24-h core process. Primary human T cells were activated with CD3/CD28 beads for 4 h and transduced with CD19 CAR/green fluorescent protein reporter (CAR/GFP) lentivirus at MOI 0.5 or 1.0 in donor-matched microfluidic-chip and static-plate comparisons. Unless otherwise stated, microfluidic rapid-manufactured CAR-T (MF-rmCAR-T) products were generated at MOI 1.0 by 20 h closed-loop recirculation. Conventionally manufactured CAR-T (cmCAR-T) products served as the product-level comparator. Day 7 CAR/GFP positivity, bulk-product vector copy number (VCN), viability, expansion, and phenotype were assessed, followed by in vitro functional testing and exploratory evaluation in a systemic Raji-Luc xenograft model. Donor-matched data were analyzed using paired t-tests or two-way repeated-measures ANOVA with Šídák correction, as appropriate. Microfluidic processing increased Day 7 CAR/GFP positivity versus matched static transduction at MOI 0.5 (14.6
Lung cancer (LC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Increasing evidence suggests that both the lung cancer-associated microbiome and the intratumoral microbiome are important components of the tumor ecosystem and contribute to cancer development, progression, and therapeutic response. Distinct microbial alterations have been identified in the lower airway, bronchoalveolar lavage fluid, airway epithelium, and tumor tissues, indicating complex host-microbe interactions across multiple microbial niches. Mechanistically, these microbial communities may influence tumor biology through microbial metabolites, chronic inflammation, immune modulation, and remodeling of the tumor microenvironment. In addition, specific microbial signatures have been associated with disease diagnosis, prognosis, recurrence, and treatment outcomes, highlighting their potential clinical value. This review integrates current advances in lung cancer-associated and intratumoral microbiota, summarizes their biological and clinical significance, and discusses key methodological challenges and future directions for clinical translation.
