Immunological Investigations最新文献

Background: Immune checkpoint inhibitors (ICIs) show clinical benefit in subsets of non-small cell lung cancer (NSCLC) patients, yet resistance remains a major challenge. Circulating tumor cells (CTCs) contribute to tumor dissemination and immune regulation. This study investigated the metabolic features of CTC subpopulations under PD-1 resistance, with a focus on the role of CD36⁺CTCs in immune evasion and pre-metastatic niche (PMN) formation.

Methods: PD-1-resistant in vitro and murine NSCLC models were established to enrich and isolate CTCs. CD36⁺ CTCs were characterized using lipid metabolomics, RNA sequencing, and functional assays. Their roles in PMN formation and immune suppression were evaluated using lung metastasis models and a tri-cell co-culture system. Fatty acid oxidation (FAO) dependency was assessed by lipid imaging, mitochondrial activity analysis, and pharmacological inhibition with etomoxir.

Results: CD36⁺ CTCs were enriched under PD-1 resistance and exhibited enhanced lipid accumulation, increased mitochondrial activity, and FAO dependency. Multi-omics analyses revealed activation of lipid metabolic pathways associated with immune suppression and extracellular matrix remodeling. Functionally, CD36⁺ CTCs promoted PMN formation and inhibited T-cell activation, while FAO inhibition significantly reduced their migratory and metastatic potential.

Conclusion: CD36⁺ CTCs drive immune evasion and metastasis in PD-1-resistant NSCLC through FAO-dependent metabolic reprogramming. Targeting this metabolic vulnerability may enhance the efficacy of immunotherapy.

Background: Pyroptosis is a highly inflammatory form of regulated cell death executed by gasdermin proteins. It promotes the release of interleukin (IL)-1β and IL-18 to support host defense, yet its dysregulation contributes to sepsis, neurodegenerative disorders, and autoimmune diseases. Many current anti-inflammatory therapies are single-target and may not restore system-level immune balance.

Objective: To summarize core pyroptosis pathways and evaluate how Traditional Chinese Medicine (TCM) modulates pyroptosis through multi-component, multi-target regulation.

Methods: We synthesize mechanistic evidence on canonical and non-canonical inflammasome cascades, focusing on caspase activation and Gasdermin D (GSDMD) cleavage. We further summarize data on representative TCM-derived compounds (berberine, curcumin, ginsenoside Rd) and a classical formula (Buyang Huanwu Decoction), emphasizing their actions on key pyroptosis nodes and upstream stress signals.

Results: Pyroptosis is driven by inflammasome-dependent signaling that activates caspases, cleaves GSDMD, and triggers pore formation with inflammatory mediator release. Evidence suggests TCM interventions can attenuate pyroptosis by converging on NLRP3 inflammasome activation, NF-κB/STAT3 signaling, and mitochondrial reactive oxygen species, while formulas may provide broader antioxidant and intercellular regulatory effects.

Conclusion: TCM offers a systems-oriented strategy for pyroptosis-centered anti-inflammatory and immunomodulatory therapy.

Background: Adjuvants potentiate adaptive immunity by enhancing antigen-specific immune responses, yet many exhibit high toxicity for clinical use. Naloxone (NLx) and naltrexone (NLt) opioid receptor antagonists have emerged as promising adjuvants in preclinical vaccination models against intracellular pathogens.

Objective: This narrative review synthesizes evidence from 2000 to 2025 evaluating NLx/NLt as adjuvants against bacterial, viral, and parasitic infections, while examining proposed immunoregulatory mechanisms.

Methods: A comprehensive search of Web of Science, PubMed, Scopus, ScienceDirect, and ProQuest employed Boolean operators combining: (vaccine OR vaccination) AND (adjuvant) AND (naloxone OR naltrexone OR NLx OR NLt OR "opioid receptor antagonist") AND ("immune response" OR "cellular immunity" OR "Th1").

Results: Key findings demonstrate that NLx/NLt monotherapy or combinatorial use with Alum consistently, enhanced Th1 polarization and cellular immunity, Elevated pathogen clearance and protection rates, synergistically overcame Alum's Th2 bias. Mechanistically, μ-opioid receptor (MOR) antagonism disrupts tonic immunosuppression, reversing opioid-mediated inhibition of dendritic cell maturation, IL-12 production, and cytotoxic T-cell function.

Conclusions: This immunorestorative action positions NLx/NLt as strategic adjuvants for vaccines targeting intracellular pathogens requiring robust cell-mediated immunity. Future horizons include combinatorial platforms (e.g. DNA vaccines + low-dose naltrexone) and clinical translation.

Background: Macrophage polarization is widely involved in the progression of acute lung injury (ALI). Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been reported to participate ininflammatory diseases by regulating macrophage polarization. This study aimed to investigate the role of BMSC-Exos in ALI through the regulation of macrophage polarization.

Methods: LPS-induced ALI mouse models and RAW264.7 cell injury models were established. Lung injury was assessed through HE staining and assessment of bronchoalveolar lavage fluid (BALF) protein contents, the lung wet/dry weight ratios, and lung myeloperoxidase (MPO) activities. The expression of protein was detected via Western blotting and immunofluorescence. Exosomes were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).

Results: BMSC-Exos significantly alleviated pathological lung injury in ALI mice; reduced the lung wet/dry weight ratio, BALF protein content, MPO activity. BMSC-Exos inhibited LPS-induced macrophage M1 polarization and reduced proinflammatory cytokine expression. The molecular mechanism revealed that the BMSC-Exos delivered miR-451a to the macrophages and that inhibition of miR-451a expression attenuated the suppressive effect of the BMSC-Exos on M1 polarization. Furthermore, miR-451a targeted MIF to inhibit the MIF/CD74 signaling pathway.

Conclusion: BMSC-Exos inhibit MIF/CD74 signaling by delivering miR-451a, thereby suppressing LPS-induced M1 macrophage polarization and alleviating ALI.

Introduction: Colorectal Cancer has been a significant health issue at a global level in terms of increasing incidence, high metastatic capacity, and inadequate treatment reactions in most patient groups. Though chemotherapy and targeted agents have given better survival chances, resistance to treatment, avoidance of the immune system as well as systemic toxicity still limit long-term efficacy. Immunotherapeutic strategies have developed as effective methods in the past few years to address these shortomings.

Methods: A comprehensive literature search was conducted across different electronics databases including Web of Science, PubMed, Scopus, and ScienceDirect utilizing keywords colorectal cancer immunotherapy, PD-1 / PD-L1, CAR-T cells, viral vector vaccines, carcinoembryonic antigen alone and in combinations.

Results: PD-1/PD-L1, CTLA-4, immune checkpoint inhibitors have shown long-term responses, especially in mismatch repair-deficient and microsatellite instability-high tumours, and cell-based therapies such as CAR -T cells and dendritic cell vaccines provide other opportunities of personalised immune modulation.

Discussion: This critical review summarizes the current developments in terms of immunotherapy and interventions of CRC with a focus on the mechanistic understanding of the issue, clinical outcomes, and combinatorial strategies aimed to improve antitumor immunity and surmount therapy resistance. Specific attention is paid to the optimization of the checkpoint blockade, innovations with vaccines and CAR-T engineering to accumulate and release tumor-specific cells and control the microenvironment. Finally, key translational challenges current clinical trials, and future perspectives are identified to promote the development of the next-generation multimodal therapies in the efficient and customized management of CRC.

Objective: To elucidate the role of the polypyrimidine tract-binding protein 1 (PTBP1)-tumor necrosis factor receptor-associated factor 6 (TRAF6) pathway in chronic obstructive pulmonary disease (COPD), with a particular focus on its regulatory effects on macrophage polarization and clearance of neutrophil extracellular traps (NETs).

Methods: A COPD-like mouse model was established via cigarette smoke (CS) exposure. Lung injury, macrophage polarization, and levels of NETs were assessed. The role of TRAF6 in macrophage polarization and NETs clearance was assessed through lentiviral modulation of TRAF6 expression. RNA immunoprecipitation-quantitative polymerase chain reaction (RIP-qPCR), RNA stability assays, and Western blotting were performed to investigate the regulatory mechanism of PTBP1 on TRAF6 expression.

Results: The COPD-like mouse model exhibited increased M1 and decreased M2 macrophage populations, along with elevated NETs formation. Both PTBP1 and TRAF6 were upregulated in lung tissues of the COPD-like mouse model and cigarette smoke extract (CSE)-treated macrophages. Mechanistically, PTBP1 bound to and stabilized TRAF6 mRNA, enhancing TRAF6 expression. Inhibition of the PTBP1-TRAF6 pathway alleviated lung injury, restored macrophage polarization balance, and promoted NETs clearance.

Conclusion: PTBP1 enhances TRAF6 expression by stabilizing its mRNA, promoting M1 macrophage polarization and impairing NETs clearance, ultimately aggravating COPD.

Background: The objective was to assess the effects of propofol on ovalbumin (OVA)-induced asthma in a mouse model and the efficacy of propofol in stabilizing mast cells and inhibiting the production of inflammatory mediators.

Methods: Animal model of asthma induced by OVA was employed to evaluate the effect of propofol. Tissues from the lungs were retrieved for HE staining. The levels of IgE, IFN-γ, MPO, and so on was deteced. Bone marrow mast cells (BMMCs) were isolated to examine the suppressive action of propofol on the degranulation.

Results: Propofol significantly reduced airway hyperresponsiveness and IgE, Th2 cytokines, and inflammatory cytokines in OVA-induced asthma model. Inhibited BMMCs degranulation and the production of inflammatory cytokines. Additionally, propofol inhibited the expression of HIF-1α and NLRP3 in asthma models. Overexpression HIF-1α in BMMCs reverses the effect of propofol. NLRP3 inhibition attenuates allergic asthma in DNP-HSA-treated DMMCs with or without overexpression HIF-1α. In terms of the mechanism, propofol interacts with HIF-1α directly, thereby disrupting HIF-1α-NLRP3 interaction and attenuating allergic asthma.

Conclusion: Propofol markedly improved OVA-induced asthma and inhibited mast cell degranulation by binding competitively to HIF-1α, thereby disrupting the HIF-1α-NLRP3 interaction and attenuating allergic asthma.

Background: Previous studies indicate associations between inflammatory cytokines and glioma, meningioma, and astrocytoma.

Methods: We conducted two-sample Mendelian randomization with genetic data for tumors from FinnGen R10 and cytokine data from GWAS. Primary analysis used inverse variance weighting, supplemented by sensitivity analyses including weighted median, simple mode, weighted mode, and MR-Egger.

Results: For glioma, TNF-related apoptosis-inducing ligand (TRAIL) was a risk factor, while Fibroblast growth factor 21 (FGF21) was protective. For meningioma, Axin-1 and Matrix metalloproteinase-1 were risk factors, whereas Fms-related tyrosine kinase 3 ligand was protective. For astrocytoma, risk factors included Eotaxin, Macrophage colony-stimulating factor 1, and Interleukin-8; protective factors were T-cell surface glycoprotein CD5 and Tumor necrosis factor ligand superfamily member 12.

Conclusions: This Mendelian randomization study identified specific inflammatory cytokines associated with these tumors, providing direction for future mechanistic research.

Background: Immune reconstitution (IR), acute graft-versus-host disease (aGVHD), and cytomegalovirus (CMV) infection are all crucial factors influencing the prognosis following hematopoietic stem cell transplantation (HSCT).

Methods: A cohort of 116 pediatric patients undergoing HSCT was divided into two groups: those with aGVHD+CMV+ (DP group) and those without this combination (NDP group). Kaplan-Meier (KM) curves were generated to compare survival differences between the groups. Logistic regression analysis was performed to identify associations between IR and aGVHD+CMV+. Cox proportional hazards regression analysis was conducted to determine the independent risk factors affecting prognosis.

Results: The prognosis of DP group was significantly worse than that of the NDP group. Notable disparities in lymphocyte subset levels were observed between the DP and NDP groups. The level of CD4-CD8-T cells showed a significant correlation with the co-occurrence of aGVHD and CMV infection. Impaired reconstitution of CD4-CD8-T cells and aGVHD+CMV+ were found to be independent risk factors for post-HSCT survival. Patients in DP group with CD4-CD8-T cell counts > 49 cells/µl (at day 90 post-HSCT) demonstrated a significantly improved prognosis.

Conclusions: Elevated CD4-CD8-T cell counts may mitigate the adverse effects of aGVHD and CMV infection on HSCT outcomes, suggesting their potential as a prognostic biomarker.