International Reviews of Immunology最新文献

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, remains a major global health concern due to its high incidence and mortality rates. Although advances in surgery, chemotherapy, and radiotherapy have improved management, the prognosis for advanced-stage HCC remains poor. Immunotherapy has emerged as a transformative approach, aiming to harness and modulate the immune system to target malignant cells more effectively. This review provides an updated overview of immunotherapeutic strategies in HCC, highlighting key modalities such as immune checkpoint inhibitors (ICIs), neoantigen-based vaccines, and tumor mutational burden (TMB) as predictive biomarkers of treatment response. Particular attention is given to ICIs targeting PD-1/PD-L1 and CTLA-4 pathways, as well as novel immune targets under investigation to overcome therapeutic resistance.

Despite encouraging clinical outcomes, significant challenges persist, including immune evasion mechanisms, limited response rates, treatment resistance, and the complexity of the immunosuppressive tumor microenvironment. Addressing these obstacles requires integrating genomic insights, artificial intelligence-driven biomarker discovery, and rational combinatorial strategies that pair ICIs with targeted agents, chemotherapy, or radiotherapy to enhance immune activation. Future directions emphasize the development of precision immunotherapy guided by molecular profiling and predictive biomarkers to improve patient stratification and treatment efficacy. This review consolidates current progress, identifies key limitations, and outlines emerging avenues to optimize the future landscape of HCC immunotherapy.

Exosomes (EXOs), membrane vesicles, have garnered significant attention in cancer treatments as a novel means by which cells communicate with each other. EXOs are recognized for their pathophysiological participation in cancer therapy and their role in immune activation. Moreover, extensive research has been conducted on EXOs-mediated cancer treatment, demonstrating significant potential for targeting cancer stem cells (CSCs). Dendritic cells (DCs), which orchestrate the immune response, have been extensively utilized in immunotherapy. Similar to other cells, DCs can release nanovesicles, predominantly EXOs. Significant attention has been directed toward dendritic cell-derived EXOs (DC-EXOs) as immunotherapeutic agents for cancer treatment. Like DCs, DC-EXOs possess chemicals that engage with immune cells, including costimulatory molecules and functional MHC-peptide complexes on their surface. DC-EXOs offer several benefits over cell-based immunotherapies that employ DCs, including the ability to facilitate immune cell-mediated tumor eradication. Tumor peptide-loaded d DC-EXOs have demonstrated efficacy in Phase I clinical studies; a Phase II clinical trial is underway. This study has examined the therapeutic potential of DC-EXOs for CSCs and various types of cancer. The advantages and disadvantages of this therapeutic method were also reviewed to augment the anticancer efficacy and targeting of DC-EXOs for prospective clinical application.

Inflammatory bowel disease (IBD) varies in prevalence globally. Recent rise in IBD cases mirrors evolving health landscape due to urbanization and lifestyle changes worldwide. Existing drugs for IBD include aminosalicylates, corticosteroids, Immunomodulators, biologics, JAK inhibitors, and antibiotics. Although these medications are effective in managing symptoms and remission, these present several with limitations. Side effects such as nausea, infections, and liver toxicity are common, and some patients may develop resistance or lose response over time. Additionally, biologics can be costly, and immunosuppressive drugs raise concerns about long-term safety along increased risk of infection. Importantly, approximately 10% to 30% of the IBD patients do not respond to conventional treatments such as corticosteroids, immunosuppressants, or biologic therapies. Research continues to explore new treatments to address these limitations and improve outcomes for individuals with IBD. This review is an attempt to critically evaluate the currently available treatments for IBD underlining their limitations, and the pressing demand for innovative strategies. Further, we delve into the rationale behind peptide-based therapies, emphasizing their potential to modulate inflammation and promote mucosal healing. The work also highlights promising outcomes from recent preclinical and clinical studies underscoring the pivotal role of peptides in IBD management.

Extracellular vesicles (EVs), nano-sized particles enclosed by a lipid membrane, play a pivotal role in cell-to-cell communication as essential mediators in various biological processes and diseases. Despite their ability to interact with multiple targets, EVs notably demonstrate a high affinity for specialized cells within the extracellular environment, particularly mononuclear phagocytes. The interaction between EVs and mononuclear phagocytes significantly affects the profile of these cells. Several factors, including vesicle cargo, size, parental cell origin, involved receptors, and the specific endocytic pathway, influence EVs' consequences and subsequent responses. Key components of mononuclear phagocytes, monocytes and macrophages, play a crucial role in the innate immune system, contributing to tissue damage, repair, remodeling, inflammation, homeostasis maintenance, and disease progression. Despite extensive research on EVs in various health and disease contexts, their precise impact on mononuclear phagocytes remains incompletely understood. Therefore, this review explores EVs' role in modulating monocyte and macrophage profiles and functions across different scenarios. It emphasizes that EVs actively shape the phenotype of these mononuclear phagocytes to maintain homeostasis and regulatory functions, but also induce pro-inflammatory polarization in infectious diseases, systemic inflammation, and autoimmunity. Simultaneously, during neoplastic or tumor development, the EV-mononuclear phagocyte axis prompts imbalanced responses, combining pro- and anti-inflammatory outcomes. These findings confirm EVs as promising tools for therapeutic strategies to modulate mononuclear phagocyte functions in diverse pathological settings.

Mitochondria serve as the powerhouses of living cells, supplying energy and essential building blocks for cellular activities. The immune system exhibits a dynamic and active characteristic within the body, wherein immune cells are constantly activated and primed for pathogens without causing harmful effects on the self-body. These characteristics necessitate that immune cells function effectively and correctly, supported by a sufficient energy supply and metabolism from the mitochondria. Mitochondrial dysfunction leads to immune dysregulation, resulting in inappropriate inflammation, autoimmunity, immunodeficiency, and hypersensitive responses, all of which contribute to the development of illness and disease. Recent studies on mitochondrial transfer in immune cells indicate that mitochondrial replacement could emerge as a promising tool for rectifying immune cell function. This review will emphasize the role of mitochondria in various immune cell types and explore how mitochondrial dysfunction can result in pathogenesis in different conditions. We also discuss the potential application of mitochondrial transfer and transplantation to- and from immune cells in the context of health and disease.

Osteoporosis is a skeletal disease that affects the microarchitecture and mineralization of the bone, reduces bone strength, and lowers bone mineral density (BMD). Post-menopausal osteoporosis (PMO), caused by estrogen deficiency, is the most common type of osteoporosis. Given the chronic nature of PMO, sustained prevention or treatment with targeted bone-specific therapies and comprehensive medical management is crucial. Long-term usage of bone-specific pharmaceutical treatment therapies that include osteoanabolic and anti-resorptive drugs has sparked questions about side effects and possible rebound occurrences following treatment termination. Therefore, new therapy approaches with fewer side effects are needed. Studies in the past decade have demonstrated that immunological factors are crucial in the onset and progression of PMO. Treg and Th17 cells have long been recognized as critical factors in maintaining bone homeostasis, mainly via regulating osteoclast differentiation. However, astonishing data from our recent studies have highlighted the significant role of Breg and Th9 cells in bone homeostasis regulation. Breg and Th9 cells directly influence the development of bone cells and also regulate the Treg-Th17 cell balance to maintain skeletal integrity. We propose that although the Treg-Th17 cell axis is undeniably important in the pathophysiology of osteoporosis, the dynamic interplay between Breg-Treg and Th9-Th17 cells may play an even more pivotal role. This broader immune network likely exerts a greater influence on bone homeostasis and the progression of osteoporosis. However, the interplay between Breg-Treg vs Th9-Th17 cell axis in PMO remains limited. This review summarizes the most recent developments regarding the Breg-Treg vs Th9-Th17 cell axis in PMO and discusses the potential novel therapeutic strategies to address this issue. Novel pathophysiological insights into the Breg-Treg-Th9-Th17 cell axis in bone metabolism may pave the way for improved diagnosis and transformative treatments for PMO.

Recurrent respiratory papillomatosis is a benign neoplastic pathology in children, young people, and adults. It causes a significant deterioration in the quality of life, with symptoms typically referred to as dysphonia and hoarseness. This disease, with variable clinical courses ranging from spontaneous resolution to dissemination of the lower airway or airway obstruction that puts the individual's life at risk, characteristically requires multiple surgical interventions. Therapy with adjuvant drugs does not yet prove the effectiveness necessary to limit the recurrence and need for surgical reoperation in this condition. The review aimed to synthesize the immunopathogenic mechanisms of relapse in recurrent respiratory papillomatosis published in the current literature and the immunological implication of risk factors and treatment.

Despite advancements in breast cancer treatment, therapeutic resistance, and tumor recurrence continue to pose formidable challenges. Therefore, a deep knowledge of the intricate interplay between the tumor and the immune system is necessary. In the pursuit of combating breast cancer, the awakening of antitumor immunity has been proposed as a compelling avenue. Tumor stroma in breast cancers contains multiple stromal and immune cells that impact the resistance to therapy and also the expansion of malignant cells. Activating or repressing these stromal and immune cells, as well as their secretions can be proposed for exhausting resistance mechanisms and repressing tumor growth. NK cells and T lymphocytes are the prominent components of breast tumor immunity that can be triggered by adjuvants for eradicating malignant cells. However, stromal cells like endothelial and fibroblast cells, as well as some immune suppressive cells, consisting of premature myeloid cells, and some subsets of macrophages and CD4+ T lymphocytes, can dampen antitumor immunity in favor of breast tumor growth and therapy resistance. This review article aims to research the prospect of harnessing the power of drugs, adjuvants, and nanoparticles in awakening the immune reactions against breast malignant cells. By investigating the immunomodulatory properties of pharmacological agents and the synergistic effects of adjuvants, this review seeks to uncover the mechanisms through which antitumor immunity can be triggered. Moreover, the current review delineates the challenges and opportunities in the translational journey from bench to bedside.

Studies in murine experimental models have made significant contributions to the understanding of asthma pathophysiology and the discovery of innovative therapeutic approaches. Nonetheless, there is a plethora of options available for selecting mouse strains, sensitization methods, challenge routes and doses, as well as approaches to evaluating host response in murine asthma model protocols. Due to the diversity of models employed, comparing results across different studies proves exceedingly challenging. The study conducted a search of pertinent PubMed articles from 2022 to April 15th, 2024. After relevant publications had been selected, the characteristics of each study were extracted, including animal strains, animal sex, sensitization methods, challenge methods, and reported outcome measures. The modeling parameters of Ovalbumin (OVA)-induced asthma model, and House Dust Mite-induced asthma model were analyzed. Additionally, we extracted data on the dose of OVA sensitization, alum administration, challenge OVA dose, and alum/sensitization OVA ratio from seven included studies. Subsequently, we conducted an analysis to determine the correlation between each of these factors and the lung resistance index (RI). This study presents an overview of the current mouse asthma models, offering valuable methodological guidance for researchers. Furthermore, this study highlights that certain parameters like sensitization dose, challenge dose, and so on, exert specific effects on the asthma lung resistance. However, there is a lack of standardized criteria and guidelines in this regard. The effects and underlying mechanisms of parameters on asthma responses remain unclear, necessitating further investigation into model parameters.

TGF-β is a pivotal cytokine that orchestrates various aspects of cancer progression, including tumor growth, metastasis, and immune evasion. In this review, we present a comprehensive overview of the multifaceted role of transforming growth factor β (TGF-β) in cancer biology, focusing on its intricate interactions with monocytes and macrophages within the tumor microenvironment (TME). We specifically discuss how TGF-β modulates monocyte and macrophage activities, leading to immunosuppression and tumor progression. We conclude with the current translational and clinical efforts targeting TGF-β, recognizing the promising role of this strategy in immunooncology.