Immunologic Research最新文献

To evaluate the efficacy and safety of natural killer (NK) cell therapy for the treatment of advanced non-small cell lung cancer (NSCLC). Relevant studies on NK cell therapy for advanced NSCLC were collected from PubMed, Scopus, Embase and the Cochrane Library up to August, 2024. Two reviewers independently screened the articles and retrieved the data using the Cochrane risk assessment tool. Meta-analysis was conducted with R (version 4.3.1). A total of nine trials were analyzed, including five phase 2 randomized controlled and four phase 1 studies. All were medium to high quality but exhibited high performance and attrition biases. NK cell treatment doses ranged from 1×10⁹ to 4×10⁹ cells for 2 or 3 cycles. In total, 324 patients with advanced NSCLC were included, comprising 199 who received NK cell therapy and 125 controls, all previously treated with platinum-based regimens. Meta-analysis demonstrated comparable disease control (OR = 2.68; 95% CI: 1.53-4.71) and 1-year survival (OR = 2.54; 95% CI: 1.28-5.02) between groups, with similar adverse events rates (OR = 1.37; 95% CI: 0.35-5.26). Subgroup analyses revealed no significant differences in efficacy. There was considerable heterogeneity among studies (I² = 0%-92.5%). Over 39 trials were registered, with only 12 marked as completed and none of the others released the outcome data. Current evidence suggests that NK cell therapy, either alone or in combination, may achieve disease control, survival outcomes and safety profiles that were comparable to existing treatments for advanced NSCLC. These findings remain exploratory and should be confirmed in larger, well-designed trials.

Autoimmune diseases are characterized by an aberrant immune response that targets the body's own tissues, resulting in chronic inflammation and organ damage. Recently, macrophage-derived exosomes (M-Exos), nanoscale vesicles that transport bioactive molecules, have gained recognition as significant mediators of immune regulation and disease progression. These exosomes possess the unique ability to traverse physiological barriers while reflecting the functional states of their originating cells. Consequently, M-Exos exert influence over various immune cell populations, including macrophages, T cells, B cells, and dendritic cells. The distinct profiles of M1- versus M2-derived exosomes illuminate their differing roles in immune activation and resolution. This review compiles current evidence regarding the involvement of M-Exos in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus, emphasizing their potential as both biomarkers and therapeutic agents. By integrating recent advancements and identifying outstanding questions, we propose a framework for employing M-Exos in diagnosis, prognosis, and personalized treatment strategies.

The recent study by Zhao et al. ( Inflamm Res. 2025) proposed a novel paradigm in which exosomal miR-125b-5p from Mycobacterium tuberculosis-infected macrophages impairs osteoblast function by targeting IGF2, thereby linking pulmonary infection to systemic osteoporosis. While this work provides a valuable mechanistic insight, our letter offers a critical appraisal to contextualize its findings and highlight pivotal unanswered questions. We posit that the proposed pathway, though compelling, requires further validation to establish direct causality in vivo, independent of the well-established role of systemic inflammatory cytokines. Furthermore, the model remains incomplete as it overlooks the potential synergistic impact of the exosomal cargo on osteoclast activation, thereby presenting only a partial view of the bone remodeling unit. Substantive questions regarding the specificity of miR-125b-5p as the sole effector, the biodistribution mechanisms of these exosomes, and their pathogen-specific nature also warrant urgent investigation. Addressing these gaps is not merely academic but is crucial for assessing the true therapeutic potential of targeting this exosomal axis in clinical practice.

This nationwide analysis quantified the contemporary and future burden of six autoimmune diseases (ADs)-rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), asthma, and psoriasis-among Mexican adolescents and young adults (AYAs, 10-24 years) using the Global Burden of Disease 2021 database. Age-standardised prevalence (ASPR), incidence (ASIR), and mortality (ASMR) rates for 2021 were calculated by direct standardisation to the GBD world population; 1990-2021 temporal patterns were explored through Joinpoint regression to derive average annual percentage change, and Box-Jenkins ARIMA models projected trends up to 2035, incorporating diagnostic-capacity covariates. In 2021, RA had the greatest burden (ASPR 45.7/100,000; ASIR 9.1), with a striking female predominance and north-south variability. Although IBD remained infrequent, its mortality rose in states where colonoscopy access expanded, suggesting detection bias yet underscoring rising severity. MS prevalence and incidence climbed steadily, particularly among young women in urbanised regions. T1DM maintained the highest absolute caseload and incidence but showed slowly declining rates; nevertheless, ASMR inched upward, reflecting suboptimal metabolic control. Asthma, while still the most prevalent AD, exhibited a modest downward trajectory, whereas psoriasis incidence was stable, yet prevalence remained substantial, signalling chronic disease accumulation. Forecasts predict moderate growth in RA and MS cases, relative plateauing of IBD, asthma, and psoriasis, and continued contraction of T1DM incidence with a slight mortality uptick. Persistent geographic and sex-related inequities highlight the necessity for region-specific prevention strategies, earlier immune-modulating therapy, and equitable access to specialised care to mitigate the projected AD burden in Mexican AYAs.

Recent advancements in vaccine technology have led to the development of RNA-based vaccines, including mRNA, circular RNA, and self-amplifying mRNA, which have emerged as a promising platform for tumor prevention and treatment. In comparison with conventional antitumor vaccines, such as whole cell, peptide, and DNA vaccines, RNA vaccines possess several advantageous characteristics. They have the capacity to encode multiple antigens, induce robust immune responses, and can be developed more expeditiously. Additionally, RNA vaccines have the potential for scalable manufacturing with acceptable safety profiles in cancer patients. Preliminary investigations, conducted both in preclinical and clinical settings, have yielded encouraging outcomes for RNA vaccines in the context of diverse tumor types. This review delineates the types, advances, and applications of RNA vaccines in antitumor therapy, as well as the challenges associated with their use. Finally, it introduces future technological directions for improving these current vaccine platforms for a wide range of therapeutic uses.

DNA methylation plays a pivotal role in the pathogenesis of Acute Lymphocytic Leukemia (ALL), a hematological malignancy marked by abnormal cellular behavior and immune dysregulation. This study aimed to investigate how alterations in DNA methylation affect lysosmal function in pediatric ALL. A total of 50 blood samples were collected from children diagnosed with ALL and analyzed for biochemical markers associated with the disease. Expression levels of key DNA methylation regulators, including DNA methyltransferase 1 (DNMT1) and DNMT3, were evaluated and compared with those from healthy controls. In addition, pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-27 (IL-27), and tumor necrosis factor-alpha (TNF-α), were monitored over a six-day period prior to treatment initiation. The study also assessed the expression of lysosome-associated membrane proteins, LAMP1 and LAMP2, which are essential for lysosomal function and the degradation of autophagosomes. To determine the DNA methylation status of the promoter regions of these genes, genomic DNA underwent sodium bisulfite treatment and digestion with methylation-sensitive and methylation-dependent restriction enzymes, followed by amplification with gene-specific primers. Our results revealed a significant upregulation of DNMT1 and DNMT3 in ALL samples, along with a marked downregulation of TET1 gene expression, which is responsible for DNA demethylation. This suggests that disrupted DNA methylation dynamics may contribute to the pathogenesis of the disease. Furthermore, methylation levels within the CpG islands of the LAMP1 and LAMP2 promoter regions were substantially elevated, showing more than a seven-fold increase in ALL samples compared to healthy control blood samples. In ALL samples, the expression levels of LAMP1 and LAMP2 were significantly reduced, may due to promoter region hypermethylation, which contributes to lysosomal dysfunction. In parallel, the expression of autophagy-related genes such as ATG5 and LC3B, markers of autophagy initiation and maturation, respectively, was markedly increased, suggesting an accumulation of autophagosomes that depend on functional lysosomes for complete degradation. Additionally, elevated levels of pro-inflammatory cytokines IL-6, IL-27, and TNF-α were consistently observed in ALL patients, indicating heightened immune activation that may drive disease progression. Collectively, these findings underscore the pivotal role of DNA methylation in disrupting lysosomal function, leading to autophagosome accumulation and impaired recycling of cytoplasmic components.

IgA nephropathy is characterized by the deposition of IgA and complement C3 in the glomerular mesangial region. Recent research has pointed out the critical role of mitochondrial damage during the occurrence and development of IgAN. During IgAN progression, elevated myc promotes the transcription of HRD1, which in turn induces the ubiquitination of MFN1, leading to mitochondrial dysfunction. We found that the expression levels of myc and HRD1 were elevated in IgAN. Down-regulation of HRD1 and myc successfully alleviated IgAN progression by promoting cell survival, reducing renal injury and improving mitochondrial homeostasis. Additionally, we observed reduced levels of MFN1 expression in IgAN. Overexpression of MFN1 significantly inhibited IgAN progression, while the deficiency of MFN1 exacerbated IgAN injury. In summary, our findings revealed that myc plays a critical role in regulating mitochondrial function in IgAN by promoting HRD1 transcription and inducing MFN1 ubiquitination. These results suggested that targeting myc/HRD1/MFN1 axis may offer a novel therapeutic strategy to combat IgAN progression.

Macrophages are the constituents of the innate immune system that play an important role in the control of infections, phagocytosis, tissue surveillance, and homeostasis. Macrophages display multiple strategies to cope with the invading microbes and prevent the spread of infections. On the other hand, many intracellular pathogens have evolved strategies to circumvent the macrophage-mediated immune responses and even thrive inside macrophages for their survival and replication. The intracellular bacteria possess a specific secretory system that secretes molecules that help regulate the host's immune responses. For example, Mycobacterium tuberculosis can successfully hide itself from the host immune system and replicate inside the host phagocytic cells with the help of chemicals secreted by its ESX secretion system. Therefore, it is necessary to deeply understand the interactions between macrophages and intracellular bacteria. This review gives insight into the biology of macrophages, inducers of antimicrobial responses in macrophages, and the secretory molecules of pathogens that aid in evading the host immune responses.

Non-small-cell lung cancer (NSCLC) is associated with high mortality. Beclin 1 (BECN1), an autophagy regulator, and ferroptosis, a lipid peroxidation-driven cell death, are both linked to cancer suppression. This study examines whether the BECN1 activator peptide, Tat-Beclin 1, induces ferroptosis in NSCLC by targeting solute carrier family 7 member 11 (SLC7A11). BECN1 expression in NSCLC tissues and cells was assessed using RT-qPCR, western blot, and immunohistochemistry. Functional assays included CCK-8 for cell viability, C11-BODIPY for lipid peroxidation, glutathione (GSH) and glutamate release, glutathione peroxidase 4 (GPX4) activity, and western blotting for iron metabolism markers (ferritin heavy chain 1 [FTH1], ferritin light chain [FTL], and transferrin receptor [TFRC]). BECN1-SLC7A11 interactions were examined using co-immunoprecipitation and immunofluorescence. BECN1 was knocked down using small hairpin RNA (shRNA), and its effects on ferroptosis were evaluated. System Xc⁻ activity was assessed in control, Tat-beclin 1, Tat-beclin 1 + shRNA-NC, and Tat-Beclin 1 + shRNA-BECN1 groups. Tumor suppression by Tat-beclin 1, erastin, and their combination was assessed in vivo using xenograft models. BECN1 expression was downregulated in NSCLC tissues and cells. Treating NSCLC cells with Tat-beclin 1 upregulated BECN1 expression and promoted ferroptosis, as evidenced by increased lipid peroxidation and malondialdehyde content, reduced GSH and GPX4 activity, and decreased cell viability, without affecting Fe²⁺ levels or the expression of iron metabolism-related proteins (FTH1, FTL, and TFRC). Knocking down BECN1 attenuated these effects, confirming its central role. BECN1 interacted with SLC7A11 to inhibit system Xc⁻, an effect abolished by knocking down BECN1. Co-treatment with Tat-beclin 1 and erastin enhanced BECN1-SLC7A11 complex formation, more strongly inhibited system Xc⁻, enhanced lipid peroxidation, inhibited the Nrf2-Keap1 signaling pathway and significantly suppressed tumor growth in vivo. Tat-beclin 1 promotes ferroptosis and tumor suppression in NSCLC by activating BECN1 and inhibiting SLC7A11-mediated system Xc⁻ activity.

In their recent study, Jedlička et al. demonstrate that glutaminase (GLS) activity is indispensable for sustaining human natural killer (NK) cell cytotoxicity, positing it as a key metabolic regulator of effector function. While this work provides a valuable foundation for understanding NK cell immunometabolism, our analysis identifies several critical areas requiring deeper exploration. This letter offers a prospective critique, highlighting the incomplete delineation of the downstream metabolic mechanisms-specifically regarding energy production, biosynthetic precursor synthesis, and redox homeostasis-that link GLS activity to the cytolytic machinery. Furthermore, we question the physiological relevance of these in vitro findings within the nutrient-deprived and competitive tumor microenvironment (TME), where NK cells must exhibit metabolic flexibility. A paramount concern is the translational double-edged sword of GLS inhibition, which may inadvertently suppress anti-tumor immunity. We conclude that future research must employ integrated multi-omics and in vivo models to resolve these complexities, which is essential for harnessing NK cell metabolism without compromising its therapeutic potential.