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Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13 + cancer-associated fibroblasts, stem-like CXCL13 + CD8 + T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13 + cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13 + CD8 + T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers., (© 2024. The Author(s).)

The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8 + T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8 + T and immune-suppressive TNFRSF4 + Treg cells in tumours might derive from peripheral CX3CR1 + CD8 + T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3 + DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3 + DCs, Treg, exhausted CD8 + T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.

Tornwaldt's cyst is an uncommon type of nasopharyngeal cyst that may cause clinically significant symptoms. We reviewed reports of 31,855 computed tomography (CT) scans and 21,158 magnetic resonance imaging (MRI) scans to ascertain how many Tornwaldt's cysts were discovered incidentally. These images had been obtained between Jan. 1, 1994, and Dec. 31, 1999, at the University of Virginia Health Sciences Center. We found that 32 Tornwaldt's cysts had been incidentally detected in 20 women and 12 men. Four of these cysts had been found on CT (0.013%; mean size: 0.66 cm3) and 28 on MRI (0.13%; mean size: 0.58 cm3). The overall rate was 0.06% (32/53,013). The most common indications for imaging in these patients were headache, seizures, dizziness/vertigo, and pharyngeal symptoms. We also report the case of a patient with a symptomatic Tornwaldt's cyst whose symptoms resolved after treatment with endoscopic marsupialization. Tornwaldt's cyst should be remembered as an uncommon but potentially treatable cause of many symptoms seen in a typical otolaryngology practice.

The MediSim system extends virtual environment technology to allow medical personnel to interact with and train on simulated casualties. The casualty model employs a three-dimensional animated human body that displays appropriate physical and behavioral responses to injury and/or treatment. Medical corpsmen behaviors were developed to allow the actions of simulated medical personnel to conform to both military practice and medical protocols during patient assessment and stabilization. A trainee may initiate medic actions through a mouse and menu interface; a VR interface has also been created by Stansfield's research group at Sandia National Labs.

We present a model for simulating casualties in virtual environments for real-time medical training. It allows a user to choose diagnostic and therapeutic actions to carry out on a simulated casualty who will manifest appropriate physiological, behavioral, and physical responses. Currently, the user or a "stealth instructor" can specify one or more injuries that the casualty has sustained. The model responds by continuously determining the state of the casualty, responding appropriately to medical assessment and treatment procedures. So far, we have modeled four medical conditions and over 20 procedures. The model has been designed to handle the addition of other injuries and medical procedures.

A compound of simple structure, 2,4-dichlorobenzyl thiocyanate (DCBT), is an antimitotic agent with a number of unusual properties. The drug causes an extreme reorganization of microtubules in cells in culture. Most normal microtubules disappear, and remaining tubulin-containing structures appear to be bundled or aggregated. DCBT irreversibly inhibits in vitro polymerization of purified tubulin, but only after a prolonged preincubation of the protein with the drug. Binding of radiolabeled DCBT to tubulin similarly requires a long incubation time, with the reaction not being complete even after 6 hr at 37 degrees C. A specific interaction with tubulin is also shown by the crossresistance to DCBT of Colcemid-resistant cells with an altered beta-tubulin. A human KB carcinoma cell line and a Chinese hamster ovary cell line selected for crossresistance to multiple chemotherapeutic agents, including most antimitotic drugs, are sensitive to DCBT. Initial structure-function studies have demonstrated weak antimitotic and antitubulin activity with the parent compound benzyl thiocyanate. Chlorination at either position 2 or position 4 of the phenyl ring produces compounds of intermediate activity (4-chlorobenzyl thiocyanate is more active than 2-chlorobenzyl thiocyanate). The thiocyanate moiety appears to be essential for activity.

Tubulin-dependent GTP hydrolysis was evaluated for its potential as a relatively simple screening assay for new antimitotic drugs. Carbamates of aromatic amines were chosen as the test system because of the relatively diverse structures of compounds in this class already known to have antimitotic properties and because of the large number of such compounds in the NSC collection of the National Cancer Institute. Of 162 compounds evaluated, significant alterations in the GTPase reaction were observed with 26 agents. Sixteen of these had substantial inhibitory effects on tubulin polymerization (true positives), while ten did not (false positives). There were no false negatives (i.e., no agent inactive in the GTPase assay inhibited tubulin polymerization). The true positives were examined for effects on cell growth and mitosis, and four compounds had 50% inhibitory concentration values of 2 microM or less with L1210 murine leukemia cells. All four caused the accumulation of cells in metaphase arrest. We conclude that tubulin-dependent GTP hydrolysis can be used effectively to select new antitubulin compounds with potential as antimitotic agents from a large group of compounds of unknown activity.