Expert Review of Clinical Immunology最新文献

Introduction: Atopic dermatitis (AD) is a common, chronic inflammatory skin disorder driven by an intricate interplay of genetic, environmental, and immunological factors.

Areas covered: As a clinically heterogenous condition, AD may be stratified into subtypes based on factors including, chronicity, immunoglobulin E levels, severity, age, and ethnicity. Transcriptomic and proteomic analyses in skin and blood help elucidate the underlying molecular mechanisms of these AD subtypes, referred to as AD endotypes. Further characterizing AD endotypes using reliable biomarkers can facilitate the development of more effective and personalized therapeutics and improve our tools for monitoring disease progression and therapeutic response across a diverse subset of patients. Here, we aim to provide perspective on the latest research regarding AD stratification using skin and blood-based studies and insight into the implications of these findings on the future of AD research and clinical practice.

Expert opinion: The precise stratification of AD endotypes will allow for the development of reliable biomarkers and a more personalized medical treatment approach. Clinical practice and trials will eventually be able to bridge clinical with molecular data to optimize individualized treatments and more effectively monitor treatment response.

Introduction: Castleman disease (CD) is a benign lymphoproliferative disease causing severe systemic inflammation. Interleukin-6 (IL-6) is a major pathogenesis of multicentric CD (MCD), but only 30-60% of patients respond to IL-6 inhibitors. Novel agents for IL-6 inhibitor-refractory cases are needed. Clinical data and samples are being collected on a large scale and the clinical, pathological, and pathogenetic aspects are being elucidated.

Areas covered: The pathological and clinical classification of CD is outlined. Focusing on idiopathic MCD (iMCD), this review identifies therapeutic targets and summarizes currently recommended drugs and promising therapeutic candidates.

Expert opinion: The pathogenesis of MCD has been implicated in the activation of the Janus kinase (JAK)-transcriptional signaling activator (STAT) 3 pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt/mechanical target of rapamycin (mTOR) signaling pathway. iMCD-TAFRO (thrombocytopenia, anasarca, fever/elevated CRP, reticulin myelofibrosis/renal dysfunction, organ enlargement) is resistant to IL-6 inhibitors, and cyclosporine and mTOR inhibitors are sometimes effective. JAK inhibitors and mTOR inhibitors may be therapeutic agents for iMCD. Recently, we have shown that peripheral helper T (Tph) cell abnormalities are at the core of iMCD pathogenesis. Therapies targeting chemokine (C-X-C motif) ligand 13 (CXCL13) produced by Tph cells and blocking the Tph-CXCL13-B cell pathway may satisfy unmet need in refractory cases.

Introduction: Giant cell arteritis (GCA) is a large vessel (LV) vasculitis that affects people aged 50 years and older. Classically, GCA was considered a disease that involved branches of the carotid artery. However, the advent of new imaging techniques has allowed us to reconsider the clinical spectrum of this vasculitis.

Areascovered: This review describes clinical differences between patients with the cranial GCA and those with a predominantly extracranial LV-GCA disease pattern. It highlights differences in the frequency of positive temporal artery biopsy depending on the predominant disease pattern and emphasizes the relevance of imaging techniques to identify patients with LV-GCA without cranial ischemic manifestations. The review shows that so far there are no well-established differences in genetic predisposition to GCA regardless of the predominant phenotype.

Expert commentary: The large branches of the extracranial arteries are frequently affected in GCA. Imaging techniques are useful to identify the presence of 'silent' GCA in people presenting with polymyalgia rheumatica or with nonspecific manifestations. Whether these two different clinical presentations of GCA constitute a continuum in the clinical spectrum of the disease or whether they may be related but are definitely different conditions needs to be further investigated.

Background: We aimed to explore simple and effective clinical parameters or combinations to predict coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease (KD).

Design and methods: This retrospective cohort study included pediatric patients with KD from January, 2013 to December, 2022. Multiple demographic and clinical data were collected, collated, and calculated from the medical records. Then they were divided into the coronary artery dilation and aneurysm formation group or the non-coronary artery dilation and aneurysm formation group. Lymphocyte-C-reactive protein ratio (LCR) was transformed into its natural logarithm and expressed as lnLCR.

Results: A total of 64 pediatric patients with KD were enrolled in this cohort study after 1:3 propensity score matching (PSM). For each unit increase in lnLCR, the possibility of coronary artery dilation and aneurysm formation decreased to 0.419 times the original value. The areas under the receiver operating characteristic (ROC) curves of lnLCR combined with albumin (ALB), ALB, and lnLCR to classify pediatric patients with KD into the coronary artery dilation and aneurysm formation group were 0.781, 0.692, and 0.743, respectively.

Conclusion: LCR combined with ALB upon admission is a promising predictor of coronary artery dilation and aneurysm formation in pediatric patients with KD.

Background: Rising cancer-related mortality underscores the importance of biomarkers for treatment and prognosis, with Chromosome Segregation 1 Like (CSE1L) linked to various cancers yet its roles remain partially understood. This study investigates CSE1L's expression and oncogenic mechanisms in solid tumors.

Research design and methods: We analyzed multi-omics data from 31 solid tumors, measured CSE1L in 41 head and neck carcinoma patients post-chemotherapy via qRT-PCR, and evaluated the impact of CSE1L knockdown on cell proliferation in A549 and HepG2 cells.

Results: In this study, we observed significantly elevated levels of CSE1L RNA in 13 tumor tissues and protein levels in 8 tumor tissues compared to their corresponding adjacent normal tissues. Additionally, our investigation unveiled a correlation between heightened CSE1L expression in tumor tissues and worsened patient prognosis, poor response to immunotherapy, and diminished effectiveness of neoadjuvant chemotherapy. Through an analysis of CSE1L mechanisms, we discovered its potential involvement in promoting tumor cell proliferation, enhancing drug resistance, and influencing immune infiltration, thereby impacting patient prognosis and treatment outcomes. Finally, we delved into the potential mechanisms underlying upregulation of CSE1L in tumor tissues.

Conclusion: Our findings demonstrate that CSE1L promotes tumor development in various malignancies, highlighting its potential as both a therapeutic target and prognostic indicator.

Introduction: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented global health challenges since its emergence in December 2019. The rapid availability of vaccines has been estimated to save millions of lives, but there is variation in how individuals respond to vaccines, influencing their effectiveness at an individual, and population level.

Areas covered: This review focuses on human genetic factors influencing the immune response and effectiveness of vaccines, highlighting the importance of associations across the HLA locus. Genome-Wide Association Studies (GWAS) and other genetic association analyses have identified statistically significant associations between specific HLA alleles including HLA-DRB1*13, DBQ1*06, and A*03 impacting antibody responses and the risk of breakthrough infections post-vaccination. Relationships between these associations and potential mechanisms and links with risks of natural infection or disease are explored, and this review concludes by emphasizing how understanding the mechanisms of these genetic determinants may inform the development of tailored vaccination strategies.

Expert opinion: Although complex, we believe these findings from the SARS-CoV2 pandemic offer a unique opportunity to understand the relationships between HLA and infection and vaccine response, with a goal of optimizing individual protection against COVID-19 in the ongoing pandemic, and possibly influencing wider vaccine development in the future.

Introduction: Esophageal cancer (EC), particularly esophageal squamous cell carcinoma (ESCC), is characterized by high incidence and poor prognosis worldwide, necessitating novel therapeutic approaches like immunotherapy. This review explores the impact of immune checkpoint inhibitors (ICIs) on ESCC, especially focusing on PD-1/PD-L1 and CTLA-4 inhibitors. Our literature search, conducted across databases including PubMed, Web of Science, and EMBASE, from January 2010 to December 2023, aimed at identifying advancements, challenges, and future directions in the use of immunotherapy for ESCC.

Areas covered: We provide a detailed analysis of clinical trials evaluating the efficacy of ICIs as monotherapy and in combination with chemotherapy, radiotherapy, and targeted therapy for locally advanced ESCC. Our findings highlight the significant survival benefits offered by ICIs, albeit with varying efficacy across patient populations, emphasizing the need for precise biomarkers to tailor treatment strategies.

Expert opinion: The integration of immunotherapy into the ESCC treatment paradigm represents a significant shift, improving survival outcomes. Future research should focus on optimizing combination therapies and novel immunotherapeutic agents, incorporating genetic and tumor microenvironment analyses to enhance patient selection and treatment efficacy.

Introduction: The advent of immune checkpoint inhibitors (ICIs) in cancer treatment has marked a transformative era, albeit tempered by immune-related adverse events (irAEs), including those impacting the musculoskeletal system. The lack of precise epidemiologic data on rheumatic irAEs is attributed to factors such as potential underrecognition, underreporting in clinical trials, and the tendency to overlook manifestations without immediate life-threatening implications, further complicating the determination of accurate incidence rates, while the complete understanding of the mechanisms driving rheumatic irAEs remains elusive.

Areas covered: This literature review comprehensively examines rheumatic irAEs in cancer patients undergoing ICI therapy, encompassing epidemiology, risk factors, mechanisms, clinical manifestations, and current management guidance for prevalent conditions such as inflammatory arthritis, polymyalgia rheumatica, and myositis. Less frequent rheumatic and musculoskeletal irAEs are also explored, alongside insights into ongoing clinical trials testing therapeutic and preventive strategies for irAEs. A thorough literature search on Medline and the National Cancer Institute Clinical Trials Database was conducted up to October 2023 to compile relevant information.

Expert opinion: In light of the evolving landscape of cancer immunotherapy, there is a compelling need for prospective longitudinal studies to enhance understanding and inform clinical management strategies for rheumatic irAEs.

Introduction: Approximately 5% of non-small cell lung cancer (NSCLC), exhibits anaplastic lymphoma kinase (ALK) rearrangements. EML4-ALK fusions account for over 90% of ALK rearrangements in NSCLC. The advent of treatment targeting ALK has significantly improved survival rates in patients with advanced ALK-positive NSCLC. However, the emergence of resistance mechanisms and the subsequent progression disease inevitably occurs. The tumor immune microenvironment (TIME) plays a pivotal role in lung cancer, influencing disease development, patient's outcomes, and response to treatments.

Areas covered: The aim of this review is to provide a comprehensive characterization of the TIME in ALK rearranged NSCLC and its intrinsic plasticity under treatment pressure.

Expert opinion: Recognizing the fundamental role of the TIME in cancer progression has shifted the paradigm from a tumor cell-centric perspective to the understanding of a complex tumor ecosystem. Understanding the intricate dynamics of the TIME, its influence on treatment response, and the potential of immunotherapy in patients with ALK-positive NSCLC are currently among the primary research objectives in this patient population.