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Topic Review
Image-Based Annotation of Chemogenomic Libraries for Phenotypic Screening
Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation of identified hits often poses a challenge. The development of small molecules with narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity or interference with basic cellular functions still pose a problem to associate phenotypic readouts with molecular targets. Hence, each compound should ideally be comprehensively characterized regarding its effects on general cell functions. Here, the researchers report an optimized live-cell multiplexed assay that classifies cells based on nuclear morphology, presenting an excellent indicator for cellular responses such as early apoptosis and necrosis. This basic readout, in combination with the detection of other general cell damaging activities of small molecules such as changes in cytoskeletal morphology, cell cycle and mitochondrial health, provides a comprehensive time-dependent characterization of the effect of small molecules on cellular health in a single experiment. The developed high-content assay offers multi-dimensional comprehensive characterization that can be used to delineate generic effects regarding cell functions and cell viability, allowing an assessment of compound suitability for subsequent detailed phenotypic and mechanistic studies.
  • 346
  • 15 Apr 2022
Topic Review
IMGG
IMGG, integrating multiple single-cell datasets through connected graphs and generative adversarial networks (GAN) to eliminate nonbiological differences between different batches. Compared with current methods, IMGG shows excellent performance on a variety of evaluation metrics, and the IMGG-corrected gene expression data incorporate features from multiple batches, allowing for downstream tasks such as differential gene expression analysis. 
  • 924
  • 25 Feb 2022
Topic Review
Immune and Tumor Microenvironment in Gliomas
Gliomas are the most common primary brain tumors. These cancers are universally fatal with limited treatment options. Glioma cells co-opt non-cancerous cells present in normal brain tissue. This manipulation results in a complex network of cell interactions. This interplay is further complicated by variations depending on specific mutations in glioma cells.
  • 270
  • 01 Jun 2023
Topic Review
Immune Cell Type-Specific Metabolic Reprogramming
Immunometabolism is an emerging discipline in cancer immunotherapy. Tumor tissues are heterogeneous and influenced by metabolic reprogramming of the tumor immune microenvironment (TIME). In the TIME, multiple cell types interact, and the tumor and immune cells compete for limited nutrients, resulting in altered anticancer immunity. Therefore, metabolic reprogramming of individual cell types may influence the outcomes of immunotherapy. Understanding the metabolic competition for access to limited nutrients between tumor cells and immune cells could reveal the breadth and complexity of the TIME and aid in developing novel therapeutic approaches for cancer.
  • 444
  • 18 Mar 2022
Topic Review
Immune Checkpoint Molecules
Antibodies against inhibitory immune checkpoint molecules (ICPMs), referred to as immune checkpoint inhibitors (ICIs), have gained a prominent place in cancer therapy. Several ICIs in clinical use have been engineered to be devoid of effector functions because of the fear that ICIs with preserved effector functions could deplete immune cells, thereby curtailing antitumor immune responses. ICPM ligands (ICPMLs), however, are often overexpressed on a sizeable fraction of tumor cells of many tumor types and these tumor cells display an aggressive phenotype with changes typical of tumor cells undergoing an epithelial-mesenchymal transition. Moreover, immune cells expressing ICPMLs are often endowed with immunosuppressive or immune-deviated functionalities. Taken together, these observations suggest that compounds with the potential of depleting cells expressing ICPMLs may become useful tools for tumor therapy.
  • 389
  • 28 Apr 2021
Topic Review
Immune System, Inflammation and Autoantigens in wAMD
Wet age-related macular degeneration (wAMD) is a chronic inflammation-associated neurodegenerative disease affecting the posterior part of the eye in the aging population. Aging results in the reduced functionality of cells and tissues, including the cells of the retina. Initiators of a chronic inflammatory and pathologic state in wAMD may be a result of the accumulation of inevitable metabolic injuries associated with the maintenance of tissue homeostasis from a young age to over 50. Apart from this, risk factors like smoking, genetic predisposition, and failure to repair the injuries that occur, alongside attempts to rescue the hypoxic outer retina may also contribute to the pathogenesis. Aging of the immune system (immunosenescence) and a compromised outer blood retinal barrier (BRB) result in the exposure of the privileged milieu of the retina to the systemic immune system, further increasing the severity of the disease. 
  • 272
  • 12 Dec 2023
Topic Review
Immune System's Role in Liver Biology and Metabolism
The liver is a remarkable organ, which coordinates a multitude of critical functions, whilst retaining the ability to dramatically remodel and regenerate damaged tissue. The liver is composed of four lobes which are subdivided into lobule structures. These are hexagonal in appearance, with each corner displaying the portal triad that consists of the portal vein, bile duct and hepatic artery. Although the liver is an exceptionally regenerative organ, chronic damage may result in scar tissue formation. This does not only have consequences for organ function but is also a major barrier for liver tissue remodeling and regeneration.
  • 372
  • 12 Jun 2023
Topic Review
Immunogenic Cell Death
Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases.
  • 966
  • 18 Feb 2021
Topic Review
Immunological Synapse and Primary Cilium
The primary cilium is a small microtubule-based organelle that extends from the apical surface of most eukaryotic cells into the extracellular space for sensing and transducing a wide range of cues. Defects in cilia growth and function are associated with a group of human inherited multisystemic diseases, known as ciliopathies. In recent years a rising number of ciliary proteins have been described at extraciliary sites, both in ciliated and non-ciliated cells, and have been implicated in cilium-independent functions and different cellular processes. Hematopoietic cells, including T lymphocytes, do not form primary cilia. However, non-ciliated T cells co-opt the ciliogenesis machinery for the assembly and function of the immunological synapse, a well-organized structure formed by immune cells – multiple types of T cells, mast cells, NK cells, B cells, neutrophils, macrophages, and dendritic cells – allowing for antigen recognition and signaling, information exchange and polarized release of molecules into the synaptic cleft. The identification of many, unexpected similarities between the primary cilium and the T cell immunological synapse at the structural, functional and molecular levels have highlighted the homology between these structures, even though they show disparate morphologies. 
  • 541
  • 11 Apr 2022
Topic Review
Immunomodulatory Effects of Histone Deacetylase 6 Inhibitors
Patients diagnosed with metastatic uveal melanoma (MUM) have a poor survival prognosis. Unfortunately for this rare disease, there is no known cure and suitable therapeutic options are limited. Histone deacetylase 6 inhibitors (HDAC6i) are currently in clinical trials for other cancers and show potential beneficial effects against tumor cell survival in vitro and in vivo. In MUM cells, HDAC6i show an anti-proliferative effect in vitro and in preclinical zebrafish xenograft models. 
  • 448
  • 05 Sep 2022
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