Expert Review of Clinical Immunology最新文献

Introduction: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death globally, characterized by an immunosuppressive tumor microenvironment (TME) that impairs immune surveillance. Immunotherapy has emerged as a transformative option; however, durable responses remain limited. The purpose of this review is to synthesize recent advances in HCC immunology, immunotherapy, and the TME.

Areas covered: Literature was identified via PubMed and ClinicalTrials.gov (January 2001-May 2025), focusing on clinical and translational studies. We outline the immunological landscape of HCC, emphasizing the roles of T cells, natural killer cells, macrophages, dendritic cells, myeloid-derived suppressor cells, and regulatory T cells in shaping tumor immunity. TME components include cancer-associated fibroblasts, tumor-associated macrophages, suppressive cytokines, angiogenesis, hypoxia, metabolic reprogramming, and the gut-liver axis. Interactions with immunotherapy, mechanisms of resistance, and combination strategies were described. Emerging biomarkers - such as tertiary lymphoid structures, PD-L1, tumor mutational burden, gene signatures, and gut microbiota - are reviewed relative to patient stratification.

Expert opinion: Immunotherapy has reshaped HCC management, but resistance, biomarker limitations, and heterogeneity remain major challenges. Advances will require TME reprogramming, multi-parametric biomarkers, and personalized strategies. Integration with targeted and locoregional approaches may achieve durable responses and move toward precision immuno-oncology, transforming HCC into a manageable or curable disease.

Introduction: Human T-lymphotropic virus type-1 (HTLV-1) is a retrovirus associated with the development of various diseases. HTLV-1 contributes to the development of several disorders that mimic autoinflammation. The pathogenic processes that underlie the emergence of such auto-inflammation-like conditions following HTLV-1 infection remain a subject of ongoing scientific debate and investigation.

Areas covered: This study provides a comprehensive review of the pathophysiology of HTLV-1-associated inflammatory diseases with an emphasis on the role of regulatory T cells and the plasticity of these cells in the development of such diseases through a selection of the most relevant and recent papers in PubMed and the Web of Science database.

Expert opinion: Recent evidence suggests that HTLV-1 infection induces the expansion of regulatory T cells (Tregs) with high plasticity, which can convert into effector T cells that promote immune deviation toward autoinflammation, including T-helper1 (Th1) cells, T-helper17 (Th17) cells and a novel effector T helper cell subpopulation with particular specificity for HAM/TSP called T_HAMs. The development of novel therapeutic strategies targeting these cells paves the way for new therapeutic strategies, which hold significant promise for providing more favorable treatment outcomes for involved individuals and ameliorating patients' symptoms.

Background: Cockroach allergens remain underrecognized in allergic diseases, despite growing evidence of their clinical impact. This study investigated cockroach sensitization prevalence in allergic rhinitis (AR) patients and its cross-reactivity with house dust mite (HDM) and seafood allergens.

Methods: 110 AR patients sensitized to at least one of eight allergens: Periplaneta americana (PA), Blattella germanica (BG), Dermatophagoides pteronyssinus (DP), Dermatophagoides farinae (DF), Blomia tropicalis (BT), shrimp, crab and squid were enrolled. Sensitization was assessed using skin prick testing (SPT) and sIgE assays and cross-reactivity by direct and inhibition enzyme-linked immunosorbent assays (ELISA).

Results: HDM allergens were the most sensitized (BT: 90%, DP: 50.9%, DF: 49.1%), followed by cockroach allergens (PA/BG: 39.1%) and seafood allergens (shrimp: 30.9%, crab: 25.5%, squid: 24.5%). sIgE testing yielded comparable results. BT demonstrated the highest prevalence. Cross-reactivity was pronounced between cockroach and HDM allergens, followed by intra-cockroach species. DP had the highest frequency of cross-reactivity among HDM allergens, while BG had a higher cross-reactivity with HDM (44.5%) than PA (40.9%). Cockroach allergens exhibited minimal cross-reactivity with seafood allergens.

Conclusions: SPT and direct ELISA performed equally, demonstrating their usefulness for assessing sensitization. Cockroach allergens interact strongly with HDM but have limited cross-reactivity with seafood.

Introduction: Eradicating measurable residual disease (MRD) may represent the final hurdle in curing ALL. The introduction of immunotherapies alone or in combination with other agents to therapies, including induction therapy, consolidation therapy, maintenance therapy, preemptive therapy and salvage therapy, was superior to chemotherapy alone in eradicating MRD during the course of treatment, leading to improved survival.

Areas covered: We provide a concise overview of the techniques used for MRD detection. We focus on the application of immunotherapies for MRD eradication at different treatment timepoints, and the factors associated with poor outcomes in patients receiving immunotherapies. We also discuss the underlying mechanisms of immunotherapy resistance in leukemia. Additionally, we highlight the importance of characterizing residual disease and designing prospective clinical trials, as these efforts may contribute to the development of novel immunotherapies and help determine which currently available immunotherapies are most effective.

Expert opinion: Immunotherapies represent a breakthrough and are currently changing the status quo of ALL therapy. Future research should focus on biomarker-directed individual immunotherapy, mechanism-driven development of new therapies, and clinical trials to identify the best immunotherapy.

Objective: Epigenetic modifications, particularly deoxyribonucleic acid (DNA) methylation, regulate the expression of immune-mediated factors. This study aimed to investigate the methylation landscape of the interleukin-10 (IL10) gene in Graves' disease (GD).

Methods: This study quantitatively profiled DNA methylation levels within the IL-10 gene using peripheral blood samples from GD patients and healthy controls. Machine learning models were constructed based on CpG methylation features to classify disease status. Furthermore, correlation between specific CpG sites methylation and clinical indicators were analyzed.

Results: This study enrolled 60 patients diagnosed with GD and 51 healthy controls. Methylation analysis revealed significantly elevated methylation at multiple IL-10 CpG sites in the GD group compared to the healthy controls (p < 0.01), forming a hypermethylated cluster. Interestingly, the newly-diagnosed GD (NGD) group also showed higher methylation at specific sites compared to the recurrent GD (RGD) group. Correlation analysis showed that methylation at chr1_206947188_R and chr1_206947135_R were positively correlated with FT3 and TRAb levels, indicating that site-specific methylation changes were associated with disease severity and immune activity in GD.

Conclusions: Our findings highlight distinct methylation patterns of the IL-10 gene in GD, with specific CpG sites carrying potential implications for disease diagnosis, stratification, and monitoring.

Introduction: Primary antibody deficiencies (PADs), especially common variable immunodeficiency (CVID), are clinically significant inborn errors of immunity due to complex phenotypes and long-term complications. This review provides an updated overview of pulmonary and gastrointestinal manifestations in PADs, focusing on CVID.

Areas covered: We conducted a structured literature review of original articles, reviews, and guidelines from the last 10 years, using databases such as PubMed and Scopus. The focus was on immunopathogenesis, clinical features, and treatment of noninfectious pulmonary and gastrointestinal complications in CVID. Key shared immunological pathways include B- and T-cell dysregulation, cytokine-driven inflammation, and microbiota alterations.

Expert opinion: Early recognition of noninfectious complications in CVID is vital to prevent organ damage and improve outcomes. A multidisciplinary, personalized approach involving genetic, immunologic, and microbiologic assessments and specialists including pathologists, pulmonologists, and gastroenterologists is essential, considering the pulmonary-gastrointestinal axis's role in mucosal immune dysfunction and systemic immune dysregulation.

Introduction: Spondyloarthritis (SpA) includes a group of chronic inflammatory disorders affecting the axial skeleton and/or peripheral joints. The Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is pivotal in cytokine-mediated signaling, contributing to SpA pathogenesis.

Areas covered: Cytokine inhibitors were the first biological therapies used in SpA. However, not all patients responded to this treatment. In this setting, Janus Kinase inhibitors (JAKi) have emerged as a promising option for SpA treatment. They act on JAK family members regulating many cytokine signaling pathways involved. Clinical trials have shown significant efficacy for the whole spectrum of SpA phenotypes. However, side effects have emerged and questions arise about their safety profile. This review explores the role of JAK-STAT pathway in SpA, focusing on its involvement in cytokine signaling and immune response regulation, its efficacy, and safety of JAKi. Thus, we searched the relevant literature in PubMed and Scopus from January 2016 until January 2025.

Expert opinion: JAKi are useful in the treatment of SpA and are recommended by international authorities in patients suffering from SpA. Despite the promising results, ongoing research is essential to assess the benefit-risk profile of JAKi in SpA.

Introduction: The demographic increase, environmental concerns, and heightened awareness about health have led Western countries to consider edible sources previously overlooked. The novelty of these sources implies a scarce knowledge about their allergenicity.

Areas covered: This review has the purpose of offering an arranged view about the allergenicity of different categories of novel foods, such as edible insects, new plant-based foods, and microalgae, by exploring cross-reactivity and common traits with other food allergies but also specific peculiarities. A particular regard is reserved for the framework in Western countries.

Expert opinion: Increasing efforts have been directed in the last years to identify dangerous cross-reactive allergens in novel foods, i.e. tropomyosin. On the other hand, eventual primary sensitizations should also be considered, especially for idiopathic anaphylaxis. In view of the partial knowledge about the allergenic potential of the novel sources, the education of the patient on this topic (particularly those with known food allergies), and an appropriate labeling of product's packages may reveal helpful to minimize the risk.

Introduction: Inborn errors of immunity (IEI) often manifest through alterations in T and B lymphocyte subsets, complicating early diagnosis and management; this review aims to synthesize current knowledge on lymphocyte subgroup dynamics in combined immunodeficiencies (CID) and related disorders.

Areas covered: We surveyed peer-reviewed literature focusing on flow cytometric profiling of T and B cell subpopulations in IEI, including both syndromic and non-syndromic presentations. Key studies were identified through systematic searches of PubMed and Embase between 2000 and 2024, emphasizing quantitative and qualitative changes in naive, central memory, effector memory, and regulatory subsets. Data extraction prioritized correlations between immunophenotypic patterns and genetic defects, clinical phenotypes, and therapeutic interventions.

Expert opinion: Detailed immunophenotyping holds transformative potential to expedite IEI diagnosis and inform individualized treatment strategies. However, widespread implementation faces barriers such as inconsistent assay standardization, limited access to high-dimensional flow cytometry in resource-constrained settings, and incomplete genotype-phenotype mapping. Future research should integrate multi-omic profiling and machine learning to refine diagnostic algorithms, enabling earlier therapeutic interventions - including targeted biologics, gene therapy, and optimized hematopoietic stem cell transplantation protocols - to improve patient outcomes.

Background: Endogenous retrovirus group E member 1 (EVA1A) is expressed in various normal tissues and plays a role in tumor development. However, its function in esophageal squamous cell carcinoma (ESCC) and immune regulation remains unclear.

Research design and methods: Bioinformatics, clinical samples, and in vivo/in vitro experiments were used to evaluate EVA1A expression and function. A co-culture system with CD8⁺ T cells, as well as a xenograft mouse model, was established. CD8⁺ T cell activity, glycolysis markers, lactate levels, and PLAU expression were assessed through flow cytometry, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent (ELISA), lactate dehydrogenase (LDH) assays, and chromatin immunoprecipitation (ChIP).

Results: EVA1A was upregulated in ESCC and negatively correlated with CD8⁺ T cell infiltration. EVA1A knockdown suppressed tumor growth and immune escape by reducing glycolysis and lactate production. Lactate promoted histone H4K12la lactylation, enhancing plasminogen activator-urokinase (PLAU) expression. PLAU overexpression reversed CD8⁺ T cell activation induced by EVA1A silencing.

Conclusion: High EVA1A expression enhances glycolysis in ESCC, and the resulting lactate further induces H4K12la lactylation and promotes PLAU expression. This inhibits the anti-tumor activity of CD8⁺ T cells, suggesting that EVA1A has potential as a therapeutic target for ESCC.