Cold Spring Harbor perspectives in medicine最新文献

Patients with relapsed or refractory pediatric solid tumors have limited therapeutic options with little to no appreciable improvements in outcomes in over two decades. Adoptive cell therapy (ACT) is a promising, targeted option for patients with the potential to minimize acute and long-term toxicities. In this review, we (1) characterize the development and manufacture different ACT approaches used for pediatric solid tumors, and (2) discuss the obstacles when targeting and treating solid tumors. The outcomes of the clinical applications of the various cell therapy products are also reviewed along with the future potential, including novel product development and combination therapies. In sum, this review serves as a comprehensive review of the clinical trial results evaluating the safety, feasibility, and efficacy of novel cell therapy products in the clinic for the treatment of pediatric solid tumors and seeks to provide new insights regarding ACT successes, failures, and challenges to benefit a rapidly expanding immunotherapy field.

Parkinson's disease (PD), once stigmatized and hidden, is now widely acknowledged by patients and recognized by the public. Yet, fundamental questions about the disease's origins, mechanisms, and progression remain unanswered. The second edition of Parkinson's Disease provides an integrated, accessible resource for clinicians and research scientists. It offers a comprehensive bench-to-bedside overview of PD, with contributions from leading experts in the clinical spectrum and the pathology, genetics, and neurobiological aspects of the condition. New chapters reflect recent advances in areas such as disease progression, biomarkers, cell-based therapies, lipid biology, and the gut-brain axis. The book emphasizes the need for interdisciplinary collaboration and serves as an educational entry point to the field and a strategic guide to future PD research.

Human immunodeficiency virus (HIV)-associated tuberculosis (TB) is a leading cause of morbidity and mortality, and HIV fuels the TB epidemic in many countries. While there is overlap, there are also critical differences in the diagnosis and management of HIV-associated TB, compared to TB in HIV-uninfected patients. To prevent deaths, the diagnosis and treatment of TB in people with HIV (PWH) needs to occur without delay. Non-sputum-based samples are important to fill the diagnostic yield gap created by challenges obtaining sputum, and reduced sensitivity of sputum diagnostics in PWH. Management of rifampicin-susceptible HIV-associated TB remains a 6month regimen initially with four drugs; an alternative 4month rifapentine and moxifloxacin containing regimen cannot be used in certain PWH (those with CD4 count <100 cells/mm³) and is currently not widely available. Management of rifampicin-resistant TB now involves a 6month all-oral regimen for most patients, including PWH. While significant gains have recently been made toward decreasing mortality from HIV-associated TB, there are many ongoing challenges, some of which are being addressed in active clinical trials.

Tuberculosis (TB) infection remains the largest reservoir sustaining the global TB epidemic and a critical target for TB elimination. Contemporary evidence has fundamentally reframed TB infection from a static latent state to a dynamic spectrum encompassing early clearance, contained infection, incipient disease, and asymptomatic TB, with heterogeneous risks of progression. This review synthesizes evidence on the natural history, epidemiology, diagnosis, treatment, and programmatic management of TB infection. It reviews World Health Organization (WHO)-recommended diagnostic tools, including interferon-γ release assays and antigen-specific skin tests, and highlights the limitations of current tests in predicting individual progression. Advances in TB preventive treatment, particularly short-course rifamycin-based regimens and evidence-based preventive therapy for drug-resistant TB exposure, are examined alongside persistent implementation gaps across the prevention cascade. The article also addresses priority populations, ethical considerations, and emerging research directions, including prognostic biomarkers, postexposure vaccines, and digital innovations. Effective TB infection management is presented as a central, integrated pillar of future TB elimination strategies.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of both dopaminergic and non-dopaminergic neurons associated with the accumulation of α-synuclein aggregates and signs of neuroinflammation. This inflammatory aspect of PD neuropathology has led to the hypothesis that the immune system, both adaptive and innate, contributes to the neurodegenerative process. While the adaptive immune system is discussed in detail in another article in this collection, this review focuses on the innate immune system, which includes monocytes, macrophages, microglia, and dendritic cells. We will also discuss the increasingly recognized link between genetic and immune response and the cross talk between peripheral and central immune cells, and its contribution to the overall immune response in PD. Finally, we will propose therapeutic strategies aimed at modulating immunity for neuroprotective and disease-modifying benefits in PD and related disorders.

Tuberculosis is an airborne infectious disease treated with combination therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial to maintain adequate blood drug level. The emergence and spread of drug-resistant Mycobacterium tuberculosis strains is mainly favored by the inadequate medical management of patients. The therapeutic approach for drug-resistant tuberculosis is cumbersome, because of the poor, expensive, less effective, and toxic alternatives to the first-line drugs. New antituberculosis regimens have been recently approved by the health authorities shortening the duration of treatment for both drug-susceptible and drug-resistant tuberculosis drugs, including new drugs such as bedaquiline, delamanid, and pretomanid. Unfortunately, they cannot represent the definitive solution to the clinical management of drug-resistant tuberculosis forms, particularly in intermediate economy settings where the prevalence of drug-resistance is high (China, India, and Former Soviet Union countries among others). Last but not least, new evidence on the burden of posttuberculosis lung disease calls for effective prevention, treatment, and rehabilitation of this form of disease. New research and development activities are urgently needed. Public health policies are required to preserve the new and old therapeutic options.

Type 1 diabetes (T1D) is a progressive T cell-mediated autoimmune disease that results from the breakdown of tolerance mechanisms in β-cell-specific T cells. Although CD8 T cells are primarily responsible for the destruction of insulin-producing β cells, intriguingly, HLA class II allelic polymorphisms confer the greatest genetic risk for the development of T1D, suggesting a critical role of CD4 T cells in disease initiation and progression. Many aspects of autoimmune T cell differentiation remain enigmatic, including where and how autoimmune CD8 and CD4 T cells arise, which molecular programs control autoimmune T cell differentiation, and how CD8 T cells sustain β-cell destruction in the face of persistent self-antigen encounter. In this work, we summarize our current understanding of β-cell-specific CD8 and CD4 T cell differentiation and function, the role of autoimmune stem-like progenitor CD8 T cells in initiating and sustaining disease, and molecular programs and key transcription factors associated with the diabetogenic T cell response.

Type 1 diabetes is an autoimmune condition in which the pancreatic β cells that produce insulin are destroyed by the body's immune system. For 100 years, diet and insulin injections have been the only effective treatment. Recent advances have led to significant progress in our understanding of the pathogenesis of the disease and the interplay between the environment, components of the immune system, and the β cells that are targeted. This has led to new therapies that rebalance the immune system and finally offer the promise of a cure.

Tuberculosis (TB) is a major cause of disease and death in young children from TB-endemic countries, especially in areas affected by poverty, social disruption, and human immunodeficiency virus (HIV) infection. This article reviews the disease burden and the natural history of disease in children with TB. It also provides guidance regarding the diagnosis, treatment, and prevention of TB in children.

The mouse provides a flexible tool to probe the interactions between the immune system and the slow growing and persistent bacterium, Mycobacterium tuberculosis (Mtb). Removal of specific cells or molecules from mice demonstrates the causal connection between these elements and control of Mtb; these connections are also seen in humans. Systems genetics, with single-cell and spatial technologies, have transformed the working model of immunity to tuberculosis (TB) in mice and humans; determining the spatiotemporal role of immune elements in immunity will allow development of targeted and precise interventions to control TB. As cure from TB is associated with lifelong health consequences, we need to also use mouse models to understand the health impact of the immune response to TB. Use of the mouse model requires precise experimental design and cautious interpretation. Rational incorporation of mouse-derived data into our working model of TB will refine our understanding of the natural history of TB worldwide.