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Tissue-resident memory T cells are increasingly being linked to human tissue-specific immune and inflammatory disease. These roles are discussed in this review.
Cua and colleagues discuss the cellular and molecular rationale for targeting IL-12 and IL-23 for therapeutic purposes in inflammatory diseases; they also review existing clinical data, discuss potential side effects, and propose future directions for targeting these cytokines in additional disorders.
Recent advances in genetics have deepened our understanding of the pathogenic mechanisms behind autoimmune and immune-mediated diseases. This has revealed both shared pathways and a considerable degree of heterogeneity between diseases.
The progress in understanding the mechanistic causes of anemias such as hemoglobinopathies and rare genetic disorders, as well as advances in therapies for anemias are reviewed.
The search for cells that can regenerate lung tissue has been fueled by the need for improved clinical therapies for treatment of lung injury or degenerative lung diseases. Emerging techniques are allowing the identification of putative stem and progenitor cells in the lung and the understanding of the molecular mechanisms regulating lung development and regeneration.
Numerous neurodegenerative diseases show deposition of protein aggregates, which are thought to cause neuronal damage. This Review discusses how cell-to-cell transmission of these pathogenic misfolded proteins is involved in initiation and progression of the disease and examines the clinical relevance of different strains in the heterogeneity of neurodegenerative disorders.
The blood-brain barrier (BBB) has a key role in maintaining brain homeostasis and, thus, brain function. This Review outlines recent advances in understanding the development and maintenance of the BBB and the contribution of BBB disruption to various neurological diseases. It also discusses how such insights might be used to design new therapeutic strategies for BBB repair.
Adjuvants play an important part in vaccines, as they can enhance and shape antigen-specific immune responses. This Review discusses the benefits of adjuvants and recent advances in understanding their mechanisms of action. The authors also set out the clinical barriers to development of new adjuvants and offer suggestions for overcoming these hurdles to the advancement of next-generation vaccines.
There has been substantial progress in understanding the role of Hedgehog (Hh) signaling in cancer in recent years, as exemplified by the approval by the US Food and Drug Administration of the Hh pathway inhibitor vismodegib in 2012 for the treatment of basal cell carcinoma. This Review outlines these advances and charts the development of Hh inhibitors, providing a critical overview of how these drugs have fared in the clinic.
Despite the initial promise of cancer therapies targeted against the epidermal growth factor receptor (EGFR), tumors treated with these agents eventually develop resistance. In this Review, the authors outline the complex mechanisms by which tumors become resistant to EGFR-targeted drugs and antibodies and offer insights into new strategies that might be employed to circumvent therapeutic resistance.
Inhibitors of RAF kinase have shown substantial benefits in the clinic for the treatment of people with BRAF-mutant melanoma, but their utility is limited by the emergence of therapeutic resistance. In this Review, the authors provide a synthesis of the currently known mechanisms of resistance to RAF-targeted therapies and show how their model has implications for the development of more effective strategies to treat patients with BRAF-mutant tumors.
Cancer cells can alter and build a permissive microenvironment that supports the malignant behavior of a growing primary tumor and developing metastases. But the role of the players in the stroma is rather complex, and their functions are intertwined, requiring a strategy to normalize the microenvironment to halt cancer progression. Re-education of stromal cells that interact with tumor cells may be a promising therapeutic avenue to exploit a genetically stable part of the tumor.
