Immunotherapy represents a paradigm shift in oncology, rooted in a century of evolving scientific understanding and clinical application. From the pioneering use of Coley’s toxins in the late nineteen Show more
Immunotherapy represents a paradigm shift in oncology, rooted in a century of evolving scientific understanding and clinical application. From the pioneering use of Coley’s toxins in the late nineteenth century to the introduction of cytokine-based interventions, the trajectory of immunotherapeutic approaches has paralleled advancements in immunology and molecular biology. This review comprehensively examines the historical development and progressive refinement of immunotherapy for cancer, charting the transition from non-specific immune stimulation to targeted immune modulation. Central to this discussion are the sophisticated mechanisms by which tumour cells evade immune detection and destruction. These include downregulation of antigen presentation machinery, secretion of immunosuppressive cytokines, recruitment of regulatory T cells and myeloid-derived suppressor cells, and exploitation of immune checkpoint pathways, particularly CTLA-4 and PD-1/PD-L1 axes. The advent of immune checkpoint inhibitors has yielded durable clinical responses in diverse malignancies, substantiating their role as foundational agents in cancer therapy. Nonetheless, both primary and acquired resistance to immune checkpoint inhibition remain significant clinical obstacles. Resistance mechanisms are multifactorial, involving tumour-intrinsic genetic alterations, modulation of the tumour microenvironment, and adaptive changes in immune cell phenotypes. Contemporary research endeavors are directed at overcoming these barriers, including the optimization of combinatorial regimens, development of next-generation checkpoint modulators, tumour-specific vaccines, and the integration of adoptive cell therapies. Future directions in cancer immunotherapy are poised to leverage advances in systems biology, genomics, and single-cell technologies to individualize interventions and enhance therapeutic efficacy. Ultimately, a comprehensive delineation of tumour-immune interactions will underpin the next generation of rational, effective, and durable cancer immunotherapies. Show less
Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical inv Show more
Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical involvement of specific mitochondrial-associated events, including mitochondrial quality control, intercellular mitochondrial transfer, and mitochondrial genetics, in potentiating the metastatic cascade of neoplastic cells. Furthermore, numerous recent studies have consistently emphasized the highly significant role mitochondria play in coordinating the regulation of tumor-infiltrating immune cells and immunotherapeutic interventions. This review provides a comprehensive and rigorous scholarly investigation of this subject matter, exploring the intricate mechanisms by which mitochondria contribute to tumor metastasis and examining the progress of mitochondria-targeted cancer therapies. Show less
Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly i Show more
Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly important role in biomedical research ranging from subcellular level to individual level. The unique properties of BICAs, including expression by cells as reporters and specific genetic modification, facilitate various in vitro and in vivo studies, such as quantification of gene expression, observation of protein interactions, visualization of cellular proliferation, monitoring of metabolism, and detection of dysfunctions. Furthermore, in human body, BICAs are remarkably helpful for disease diagnosis when the dysregulation of these agents occurs and can be detected through imaging techniques. There are various BICAs matched with a set of imaging techniques, including fluorescent proteins for fluorescence imaging, gas vesicles for ultrasound imaging, and ferritin for magnetic resonance imaging. In addition, bimodal and multimodal imaging can be realized through combining the functions of different BICAs, which helps overcome the limitations of monomodal imaging. In this review, the focus is on the properties, mechanisms, applications, and future directions of BICAs. Show less
Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we re Show more
Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we recount the evidence identifying the basic leucine zipper transcription factors ATF5, CEBPB, and CEBPD as targets for brain and other malignancies. We describe strategies that exploit the structures of the three factors to create inhibitory dominant-negative (DN) mutant forms that selectively suppress growth and survival of cancer cells. We then discuss and compare four peptides (CP-DN-ATF5, Dpep, Bpep and ST101) in which DN sequences are joined with cell-penetrating domains to create drugs that pass through tissue barriers and into cells. The peptide drugs show both efficacy and safety in suppressing growth and in the survival of brain and other cancers in vivo, and ST101 is currently in clinical trials for solid tumors, including GBM. We further consider known mechanisms by which the peptides act and how these have been exploited in rationally designed combination therapies. We additionally discuss lacunae in our knowledge about the peptides that merit further research. Finally, we suggest both short- and long-term directions for creating new generations of drugs targeting ATF5, CEBPB, CEBPD, and other transcription factors for treating brain and other malignancies. Show less