Background Dendritic cells (DCs) are professional antigen presenting cells (APCs), which can activate antigen-specific CD8+ T cell immunity, resulting in tumor clearance. Immature DCs are usually stimulated by various adjuvants through their immune receptors. Among them, Toll-like receptor 4 (TLR4) has an important role in activating DCs to cause their maturation. In fact, TLR4 is well-known to induce innate and adaptive immune responses against various external microbial or internal damage associated molecular patterns (DAMP). LPS is widely regarded as a strong stimulator of TLR4 signaling. However, LPS is inappropriate for use in humans since it is an endotoxin. Unfortunately, other TLR4 ligands such as HMGB1 or heat shock proteins have weak adjuvant effects. Therefore, there is a need to identify novel, biocompatible, strong, TLR4 ligands. Methods 40S ribosomal protein S3 (RPS3) was screened through pull-down assay using TLR4. BMDCs from wild type (WT) and TLR4 knock-out mice were treated by RPS3 to identify the activation and maturation of DCs. T cell generation including memory T cells, tumor prevention, and treatment experiments were performed with BMDCs based vaccination. Also, human DCs originated from patients were treated by RPS3 to confirm the activation and maturation of DCs. Results In this study, we identified 40S ribosomal protein S3 (RPS3) through a pull-down assay using a variety of human cancer cell-derived proteins that could bind to TLR4. RPS3 was released from tumor cells following treatment with an anticancer drug, and it was shown that the released RPS3 binds to TLR4. Recombinant RPS3 induced maturation and activation of DCs, and following pulsing with tumor specific antigens, these DCs could be used as a vaccine to significantly increase tumor specific CD8⁺IFN-γ⁺ T cells, and provide both tumor prevention and tumor treatment effects. The effect of RPS3 on DC maturation and its utility as a vaccine were shown to be dependent on TLR4 using TLR4 knockout mice. Conclusions This study therefore proved that human cancer cell-derived RPS3, a novel TLR4 ligand, has great potential as an adjuvant in tumor-specific antigen DC-based vaccines.

Carfilzomib is mainly used to treat multiple myeloma. Several side effects have been reported in patients treated with carfilzomib, especially those associated with cardiovascular events, such as hypertension, congestive heart failure, and coronary artery disease. However, the side effects, especially the manifestation of cardiovascular events through capillaries, have not been fully investigated. Here, we performed a pilot experiment to monitor peripheral vascular dynamics in a mouse ear under the effects of carfilzomib using a quantitative photoacoustic vascular evaluation method. Before and after injecting the carfilzomib, bortezomib, and PBS solutions, we acquired high-resolution three-dimensional PAM data of the peripheral vasculature of the mouse ear during each experiment for 10 h. Then, the PAM maximum amplitude projection (MAP) images and five quantitative vascular parameters, i.e., photoacoustic (PA) signal, diameter, density, length fraction, and fractal dimension, were estimated. Quantitative results showed that carfilzomib induces a strong effect on the peripheral vascular system through a significant increase in all vascular parameters up to 50%, especially during the first 30 min after injection. Meanwhile, bortezomib and PBS do not have much impact on the peripheral vascular system. This pilot study verified PAM as a comprehensive method to investigate peripheral vasculature, along with the effects of carfilzomib. Therefore, we expect that PAM may be useful to predict cardiovascular events caused by carfilzomib.

Background: Paraspinal schwannomas arising from exiting lumbar nerve roots are uncommon but clinically important because deep intramuscular extension can obscure tumor boundaries. In multilobulated lesions, an intraoperative declaration of gross-total resection (GTR) based on direct visualization alone can be misleading. Case Description: A 60-year-old man presented with 12 months of progressive left anterolateral thigh pain and numbness [Visual Analogue Scale (VAS) 6/10; Oswestry Disability Index (ODI) 70%] without motor deficit. Magnetic resonance imaging (MRI) demonstrated a large, predominantly extraforaminal/paraspinal dumbbell schwannoma from L1 to L2 (30 mm × 43 mm × 72 mm; ellipsoid volume approximately 48.6 cm³). Computed tomography (CT)-guided biopsy confirmed schwannoma [World Health Organization (WHO) grade 1]. Microsurgical excision was performed via a posterior paramedian (Wiltse) muscle-splitting corridor with limited L1–L2 hemilaminectomy and continuous neurophysiological monitoring. Recovery was uncomplicated with complete symptom resolution by 2 months (VAS 0; ODI 0%). Nevertheless, contrast-enhanced MRI demonstrated a residual enhancing nodule (15 mm × 22 mm × 23 mm; ellipsoid volume approximately 4.0 cm³), approximately 8% (8.2%) of the initial tumor volume. Conclusions: Occult residual tumor can persist after apparent GTR and complete clinical recovery. We propose VERIFY-GTR: a proposed, auditable end-of-resection verification bundle coupled with an early postoperative contrast-enhanced MRI baseline (ideally within 48–72 hours when feasible) to define a combined surgical plus radiologic endpoint for radiologically verified GTR, avoid premature finalization of GTR status based on intraoperative inspection alone, and to guide surveillance intensity.