Macrophages employ quorum licensing to regulate collective activation.

Macrophage-initiated inflammation is tightly regulated to eliminate threats such as infections while suppressing harmful immune activation. However, individual cells' signaling responses to pro-inflammatory cues are heterogeneous, with subpopulations emerging with high or low activation states. Here, we use single-cell tracking and dynamical modeling to develop and validate a revised model for lipopolysaccharide (LPS)-induced macrophage activation that invokes a mechanism we term quorum licensing.

Regulation of the IL-10-driven macrophage phenotype under incoherent stimuli.

Macrophages are ubiquitous innate immune cells that play a central role in health and disease by adopting distinct phenotypes, which are broadly divided into classical inflammatory responses and alternative responses that promote immune suppression and wound healing. Although macrophages are attractive therapeutic targets, incomplete understanding of this functional choice limits clinical manipulation. While individual stimuli, pathways, and genes involved in macrophage functional responses have been identified, how macrophages evaluate complex in vivo milieus comprising multiple divergent stimuli remains poorly understood.

Thoracic epidural blood patch with high volume blood for cerebrospinal fluid leakage of cervical spine (C2-3) complicated with spontaneous intracranial hypotension.

Acute and chronic subdural hemorrhage in a 33 year old woman with severe headache from occipital to frontal regions and dull neck pain was diagnosed on magnetic resonance image, which revealed cerebrospinal fluid leakage at C2-3 with spontaneous intracranial hypotension. Successful treatment was performed by epidural blood patch from the level of T7-T8 with injection of 20 mL of autologous blood.

Spatial and functional heterogeneities shape collective behavior of tumor-immune networks.

Tumor growth involves a dynamic interplay between cancer cells and host cells, which collectively form a tumor microenvironmental network that either suppresses or promotes tumor growth under different conditions. The transition from tumor suppression to tumor promotion is mediated by a tumor-induced shift in the local immune state, and despite the clinical challenge this shift poses, little is known about how such dysfunctional immune states are initiated. Clinical and experimental observations have indicated that differences in both the composition and spatial distribution of different cell types and/or signaling molecules within the tumor microenvironment can strongly impact tumor pathogenesis and ultimately patient prognosis.

Engineered cell-based therapies: a vanguard of design-driven medicine.

Engineered cell-based therapies are uniquely capable of performing sophisticated therapeutic functions in vivo, and this strategy is yielding promising clinical benefits for treating cancer. In this review, we discuss key opportunities and challenges for engineering customized cellular functions using cell-based therapy for cancer as a representative case study. We examine the historical development of chimeric antigen receptor (CAR) therapies as an illustration of the engineering design cycle.