Advances in Immunology最新文献

Fungal infections are increasingly recognised as a major threat to global human health, with several million preventable deaths each year now attributable to fungal diseases. Climate change, global pandemics and increased use of antibiotics and immune-suppressing drugs in modern medicine have all contributed towards recent rises in the number of cases of life-threatening fungal infections. To circumvent these trends, it is imperative that we develop a deeper understanding of the immune responses that operate to protect against fungal invasion if we are to develop adjunctive immune-based therapies for these infections. Recent work has already demonstrated how mechanistic insights into antifungal immune responses can yield therapeutic benefits. This chapter covers the major processes, cells and receptors that are required for successful antifungal immune responses, focusing on recent developments that have driven significant new step-changes in our understanding of how these pathogens are detected and removed from the body.

Cancer's complex nature and personal variety make it among the toughest cancers to conquer. Innovative treatment strategies can be achieved through new biotechnology developments. DNA and mRNA vaccinations deliver an opportunity to take a new path for cancer. The ways in which DNA and mRNA vaccinations generate immune reactions that specifically focus on cancer cells are discussed in this section. This chapter focuses on the development and creation of these vaccines. We will focus on the latest research that proves the effectiveness of these vaccines and their safety over different types of cancer. Also, we discuss the technological and biological barriers in the process of vaccine development that hinder the development of these vaccines, such as the stability of delivery methods and a patient-specific design for vaccines. DNA and mRNA vaccinations are an important therapeutic approach against cancer with genetic information. They offer an opportunity for the future to develop tailored as well as more efficient treatment options.

The emergence of mRNA-based cancer immunotherapy has transformed the avenue of cancer treatment, offering an innovative strategy that leverages the body's immune system to identify and eradicate tumor cells selectively. Effective delivery of mRNA to specific organs and cells is limited by its instability, low cellular uptake efficiency, and degradation during extracellular transport and endosomal escape. Significant advancements in nanoparticle design have driven the rapid progress of mRNA-based immunotherapies. Nanocarriers have emerged as vital delivery systems, providing enhanced stability, resistance to enzymatic degradation, and efficient mRNA delivery to target cells. This chapter investigates the design, synthesis, and functionalization of different types of nanoparticles, including lipid-based, polymeric, and hybrid nanoparticles and also highlights their unique characteristics and mechanisms for mRNA delivery in cancer immunotherapy. This chapter explores cellular uptake mechanisms, strategies for endosomal escape, and the subsequent translation of mRNA into therapeutic proteins that elicit a vigorous anti-tumor immune response. Recent advances in nanoparticle-based mRNA vaccines are also explored, with an emphasis on research findings and clinical trials that reveal both their potential and challenges. The chapter aims to provide a thorough overview of nanoparticle integration in mRNA-based cancer immunotherapy and also offer insights into future developments and emerging trends in the field.

Cancer immunotherapy recently has emerged as a revolutionary method in oncology. It takes the help of the body's immune system in fighting against tumor cells. Amongst the various approaches, DNA and mRNA vaccines are novel modalities with the potential to revolutionize cancer treatment. They represent one such approach that can result in potent immune responses against tumor-specific antigens. The few but serious translation bottlenecks at the clinical level have been related to stability, in vivo distribution, and efficient delivery systems for DNA and mRNA vaccines. It is against this salient background that this chapter takes readers through recent success stories of DNA and mRNA vaccines, right from the formulation of the vaccine to delivery mechanisms, stability, and bioavailability in cancer immunotherapy. The further challenges that are discussed in this chapter are those of effect in vivo distribution and how such challenges impact therapeutic efficacy. In addition, the new emerging technologies for in vivo distribution and opportunities for optimization of emerging vaccines to clinical use are approached, with the main focus placed on new delivery platforms. The aim of this chapter is to help understand the current landscape and future directions toward DNA and mRNA vaccines in designing more effective and personalized cancer therapies.

Malignant melanoma is one of the most aggressive forms of cancer and a leading cause of death from skin tumors. With the rising incidence of melanoma diagnoses, there is an urgent need to develop effective treatments. Among the most modern approaches are cancer vaccines, which aim to enhance cell-mediated immunity. Recently, mRNA-based cancer vaccines have gained significant attention due to their rapid production, low manufacturing costs, and ability to induce both humoral and cellular immune responses. These vaccines hold great potential in melanoma treatment, yet their application faces several challenges, including mRNA stabilization, delivery methods, and tumor heterogeneity. The recent success of mRNA vaccines in combating COVID-19 has renewed interest in their potential for cancer immunotherapy. In particular, mRNA cancer vaccines offer high specificity and better efficacy compared to traditional treatments. They can target tumor-specific neoantigens, prompting a robust immune response. This chapter reviews the mechanism of action of mRNA vaccines, advancements in adjuvant identification, and innovations in delivery systems such as lipid nanoparticles. It also discusses ongoing clinical trials evaluating the efficacy of mRNA-based vaccines in melanoma, highlighting promising early-phase results. Despite their potential, the development of mRNA cancer vaccines faces significant obstacles. Tumor heterogeneity, immunosuppressive tumor microenvironments, and practical issues like vaccine administration and clinical evaluation methods are major barriers to success. By addressing these challenges and advancing innovations, mRNA cancer vaccines hold promise for transforming melanoma treatment. A careful balance between the opportunities and challenges will be key to unlocking the full potential of mRNA vaccines in cancer immunotherapy.

Macrophages are now recognised to be highly heterogeneous, with diverse ontogenies, anatomical locations and characteristics, all of which inform their function. Nerve-associated macrophage subpopulations have been found to exist across tissues, and whilst they appear to have roles in neuronal maintenance and repair, their function is still being elucidated. Although nerve-associated macrophage functions in the Central Nervous System have taken centre-stage, nerve-associated macrophages also interact with peripheral nerves and this field remains relatively understudied. This review discusses recent studies into nerve-associated macrophages across peripheral tissues. These studies identify populations of nerve-associated macrophages in many peripheral tissues, and reveal elegant neuroimmune communication pathways which coordinate functions from infection defence and anti-inflammatory actions to neuronal maintenance for homeostatic tissue function and nerve repair. We highlight nerve-associated macrophage interactions with nerves in peripheral tissues as a rapidly evolving field which could revolutionise our understanding of macrophage function in both homeostasis and disease.

This chapter focuses on the groundbreaking advances in the treatment of cancer via the development of innovative immunotherapies, which include immune checkpoint inhibitors, bispecific antibodies, and cancer vaccines. The chapter begins with an overview of current cancer treatment paradigms and the pressing need for innovative therapeutic strategies. It then explores the principles and latest trends in immunotherapy, highlighting the mechanisms of action and key players in checkpoint blockade therapy. The discussion extends to bispecific antibodies, focusing on their unique mechanisms, developmental challenges, and current clinical applications. The chapter also explores the frontier of cancer vaccines, distinguishing between preventive and therapeutic approaches, and examining the development of personalized vaccines. Finally, the chapter provides insights into future directions in cancer treatment, offering a comprehensive perspective on the evolving landscape of immunotherapy and its potential to transform patient outcomes.

Vaccination is one of the most effective medical interventions, saving millions of lives and reducing the morbidity of infections across the lifespan, from infancy to older age. The generation of plasma cells and memory B cells that produce high affinity class switched antibodies is central to this protection, and these cells are the ultimate output of the germinal centre response. Optimal germinal centre responses require different immune cells to interact with one another in the right place and at the right time and this delicate cellular ballet is coordinated by a network of interconnected stromal cells. In this review we will discuss the various types of lymphoid stromal cells and how they coordinate immune cell homeostasis, the induction and maintenance of the germinal centre response, and how this is disorganised in older bodies.

Recent advances in human genomics technologies have helped uncover genetic risk alleles for many complex autoimmune diseases. Intriguingly, over 90% of genome-wide association study (GWAS) risk alleles reside within the non-coding regions of the genome. An emerging new frontier of functional and mechanistic studies have shed light on the functional relevance of risk alleles that lie within long noncoding RNAs (lncRNAs). Here, we review the mechanisms and functional implications of five evolutionarily conserved lncRNAs that display risk allele association with highly prevalent autoimmune diseases.

The innate immune system uses a distinct set of germline-encoded pattern recognition receptors to recognize molecular patterns initially thought to be unique to microbial invaders, named pathogen-associated molecular patterns. The concept was later further developed to include similar molecular patterns originating from host cells during tissue damage, known as damage-associated molecular patterns. However, recent advances in the mechanism of monogenic inflammatory diseases have highlighted a much more expansive repertoire of cellular functions that are monitored by innate immunity. Here, we summarize several examples in which an innate immune response is triggered when homeostasis of macromolecule in the cell is disrupted in non-infectious or sterile settings. These ever-growing sensing mechanisms expand the repertoire of innate immune recognition, positioning it not only as a key player in host defense but also as a gatekeeper of cellular homeostasis. Therapeutics inspired by these advances to restore cellular homeostasis and correct the immune system could have far-reaching implications.