Background: The obesity paradox is a topic of increasing interest in oncology and epidemiology research. Although this phenomenon has been observed in melanoma patients receiving immune checkpoint inhibitors, little is known about its mechanism. We aim to investigate the prognostic value of obesity and its association with adiposity and systemic inflammation. Methods: This retrospective study evaluates the data of patients who received pembrolizumab or nivolumab for unresectable or metastatic melanoma between June 2015 and April 2021. The skeletal muscle index (SMI) and visceral fat index (VFI) (cm²/m²) were calculated by dividing the cross-sectional areas of skeletal muscle and visceral fat by height squared. The systemic immune-inflammation index (SII) was defined as the total peripheral platelet count×neutrophil/lymphocyte ratio. Cox proportional hazard regression analysis was conducted to determine the association with overall survival. Results: We analyzed 266 patients with a median age of 60 years (IQR 51–69 years; 135 men and 131 women). The protective effect of obesity was independent of covariates (HR 0.60; 95% CI 0.37 to 0.99; p=0.048), but disappeared after adjusting for VFI (HR 0.76; 95% CI 0.41 to 1.40; p=0.380) or SII (HR 0.71; 95% CI 0.42 to 1.18; p=0.186). An increase of 10 cm²/m² in VFI was associated with longer overall survival after adjusting for covariates (HR 0.88; 95% CI 0.79 to 0.99; p=0.029). The prognostic value of VFI remained and predicted favorable overall survival after additional adjustment for SMI (HR 0.86; 95% CI 0.76 to 0.98; p=0.025), but disappeared with adjustment for SII (HR 0.92; 95% CI 0.82 to 1.03; p=0.142). An increase of 100×10⁹/L in SII was associated with poor overall survival when adjusted for covariates (HR 1.08; 95% CI 1.05 to 1.11; p<0.001) or when additionally adjusted for VFI (HR 1.07; 95% CI 1.04 to 1.10; p<0.001). Conclusions: Visceral adiposity and systemic inflammation are significant prognostic factors in patients with unresectable or metastatic melanoma receiving immune checkpoint inhibitors. The prognostic impact of visceral adiposity is dependent on systemic inflammation status.

A 3D PNS disease–on–a–chip enables the monitoring of pathophysiological processes, including demyelination and remyelination.

Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXO ^Ascites ) in cancer progression and use modified exosomes as resources for cancer therapy. EXO ^Ascites from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXO ^Ascites concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In MET -amplified GC, EXO ^Ascites contain abundant MET; their selective delivery to tumor cells enhanced angiogenesis and invasiveness. Exosomal MET depletion substantially reduced invasiveness; an additive therapeutic effect was induced when combined with MET and/or VEGFR2 inhibition in a patient-derived MET -amplified GC model. Allogeneic MET-harboring exosome delivery induced invasion and angiogenesis in a MET non-amplified GC model. MET -amplified patient tissues showed higher exosome concentration than their adjacent normal tissues. Manipulating exosome content and production may be a promising complementary strategy against GC.

Microfluidics have enabled a wide range of experimental possibilities in the field of neuroscience. Unfortunately, the wider scale adoption of polydimethylsiloxane (PDMS) based microfluidic devices faces challenges due to inherent material compatibility issues and lack of standardized manufacturable devices. In this work, we present an injection molded plastic array three-dimensional (3D) neuron culture platform (Neuro-IMPACT) made of polystyrene (PS) with a standard 96-well plate form factor that can recapitulate elements of both the central and peripheral nervous systems. A standardized in vitro platform for neuron culture will facilitate the development of new therapies for neurodegenerative diseases, as they would enable quantitative analysis based on imaging as well as biochemical analysis. To demonstrate the versatility of Neuro-IMPACT, we modeled physiologically relevant complex co-culture models such as a 3D neuronal network, blood–brain barrier, and myelination. The Neuro-IMPACT offers a high-throughput screening compatible platform with the ability to engineer the neuronal microenvironment to aid both basic and applied neuroscience research.

In vitro platforms for studying the human brain have been developed, and brain organoids derived from stem cells have been studied. However, current organoid models lack three-dimensional (3D) vascular networks, limiting organoid proliferation, differentiation, and apoptosis. In this study, we created a 3D model of vascularized spheroid cells using an injection-molded microfluidic chip. We co-cultured spheroids derived from induced neural stem cells (iNSCs) with perfusable blood vessels. Gene expression analysis and immunostaining revealed that the vascular network greatly enhanced spheroid differentiation and reduced apoptosis. This platform can be used to further study the functional and structural interactions between blood vessels and neural spheroids, and ultimately to simulate brain development and disease.